Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin.We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting...Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin.We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting nephrotic syndrome.Genetic analysis of fibronectin 1 gene showed heterozygosity for the Y973C mutation.However,this mutation was not found in her parents.She had stable renal function but persistent nephrotic proteinuria after one-year follow-up.展开更多
An understanding of osteoblast adhesion and proliferation on biomaterials is crucial to optimizing the surfaces of artificial implants used in clinical practice. Polished, anodic oxidation （AO） and micro-arc oxidati...An understanding of osteoblast adhesion and proliferation on biomaterials is crucial to optimizing the surfaces of artificial implants used in clinical practice. Polished, anodic oxidation （AO） and micro-arc oxidation （MAO） treated titanium （Ti） plates were used as model surfaces to study the adhesion of MG-63 cells. Cells were monitored for 0.5 and 4 h; faster adhesion and spreading of MG-63 ceils were observed on the AO and MAO modified samples. Stimulated secretion of fibronectin （FN） influenced the adhesion rates. In addition, AO and MAO modified surfaces promoted cell proliferation through apparent up-regulation of FN and integrin a5 transcription via outside-in signaling. This strongly suggests that FN secretion by osteoblasts plays an essential role in enhanced cell adhesion, spreading and proliferation on these modified Ti surfaces.展开更多
Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective f...Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.展开更多
Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the...Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.展开更多
Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an ...Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.展开更多
AIM To investigate the adjusting effects of the Yanggan Jieyu (YGJY, nourishing the liver and alleviate mental depression) decoction on the plasma concentration of fibronectin (FN), fibronectin receptor (FNR), tumor ...AIM To investigate the adjusting effects of the Yanggan Jieyu (YGJY, nourishing the liver and alleviate mental depression) decoction on the plasma concentration of fibronectin (FN), fibronectin receptor (FNR), tumor necrosis factor alpha (TNF α) and the activity of interleukin 1 (IL 1) in patients with cirrhosis. METHODS Thirty four cases of cirrhosis (in decompensation) were divided into YGJY decotion treated group and control group treated by routine method. FN, FNR and TNF α were measured with ELESA and expressed as mg/L (FN, FNR) and ng/L (TNF α), and IL 1 was measured by mice thymocyte proliferation using β scintillation counter and expressed as cpm. RESULTS In YGJY decoction treated group, before treatment, FN was 247 9±97 2, FNR 5 6±2 7, TNF α 83 9±7 1 and IL 1 was 2760 8±813 6, and after treatment. FN was 298 3±93 2 ( P <0 01), FNR 4 3±2 3 ( P <0 05, TNF α 93 6±12 0 ( P <0 05) and IL 1 was 1922 3±847 0 ( P <0 05). The FN and TNF α plasma level after treatment increased remarkably, while FNR and IL 1 decreased obviously. In the control group before treatment, FN was 248 8±101 9, FNR 5 5±1 9, TNF α 126 1±48 1 and IL 1 was 2540 6±603 2, and after treatment was 241 6±77 1 ( P >0 05), FNR 5 4±1 2 ( P >0 05), TNF α 100 6±15 5 ( P >0 05) and IL 1 was 2360 6±860 0 ( P >0 05), the plasma levels of FN, TNF α, FNR and IL 1 did not change signifiantly. CONCLUSION YGJY decoction could prevent the process of the hepatic fibrosis by readjusting the plasma levels of FN, FNR, TNF α and IL 1 mediating acivities in cirrhosis, which is of clinical significance.展开更多
Objective To investigate the expression and change of the β3 integrin subunit and fibronectin in normal human oviductal tissue during various phases of the menstrual cycle and tubal ectopic pregnant tissueMethods Sam...Objective To investigate the expression and change of the β3 integrin subunit and fibronectin in normal human oviductal tissue during various phases of the menstrual cycle and tubal ectopic pregnant tissueMethods Samples of normal ( n=29 ) and pregnant fallopian tube ( n=22 ) tissues were obtained from women who had normal cycle and history of normal pregnancy. Normal oviductal tissue samples were divided into 4 groups based on their menstrual cycle. Both expression and distribution of the β3 subunit and fibronectin were determined with the immunohistochemical method and the image analysis.Results The β3 subunit was expressed in the cytoplasm of ciliated cells. The expression level of the β3 subunit was higher after ovulation than that before ovulation in isthmus epithelium (P<0.001), and declined significantly after ovulation in ampullae epithelium (P<0.001). In umbrella epithelium within 4 days after ovulation, the expression level of the β3 subunit was observed at rather higher level among other phases (P <0.001). The ciliated and secretory cells of the epithelium except for where the pregnancy occurred in tubal pregnancy expressed the β3 subunit, and no significant relationship was found between the normal tubal tissue of the secretory phase and tubal ectopic pregnant tissue (P>0.05). Fibronectin was expressed in the basement membrane of human oviductal epithelium and matrix. The expression level of fibronectin was higher in the hyperplastic phase than that in the secretory one (P<0.001). And it was lower in normal tubal tissue of the secretory phase than that in tubal ectopic pregnant tissue (P<0.001).Conclusion Theβ3 integrin subunit was expressed in the ciliated cells of human oviductal epithelium, and fibronectin was expressed in the basement membrane of human oviductal epithelium and matrix. Their expression and change in oviductal tissue is based on different phases of menstrual cycle. The β3 subunit could not related to the occurrence of tubal ectopic pregnancy. Fibronectin could be the potential molecular basis for the tubal ectopic pregnancy.展开更多
AIM: To determine the effects of a low dose latrunculin (LAT)-A on dexamethasone (Dex)-induced upregulation of extracellular matrix proteins fibronectin (FN) in cultured human trabecular meshwork (HTM) cells. METHODS:...AIM: To determine the effects of a low dose latrunculin (LAT)-A on dexamethasone (Dex)-induced upregulation of extracellular matrix proteins fibronectin (FN) in cultured human trabecular meshwork (HTM) cells. METHODS: HTM cells were cultured to confluent and incubated with 0.4 mu mol/L Dex and/or 0.05 mu mol/L LAT-A. FN expression in HTM cells was evaluated by Western blot and immunofluorescence microscopy. RESULTS: Dex up-regulated FN production in HTM cells, failed to do so when co-incubated with LAT-A. LAT-A decreased production of FN in cultured HTM cells. CONCLUSION: This study indicated that LAT-A may modulate the expression of fibronectin in trabecular meshwork to achieve treatment for steroids and other types of glaucoma. It has an important prospect as an intraocular pressure-lowering drug.展开更多
AIM To investigate the effect of endotoxin on liver fibrosis and further define the role of hepatocytes in production of fibronectin in primary liver cell culture by endotoxin.METHODS After isolation and seeding of he...AIM To investigate the effect of endotoxin on liver fibrosis and further define the role of hepatocytes in production of fibronectin in primary liver cell culture by endotoxin.METHODS After isolation and seeding of hepatocytes, the obtained cells were added to various doses (0, 5, 10, 15 and 20mg/L) of LPS treated culture media. The cells were collected and counted at various periods (0, 12, 24, 48, 72, 96, 120h). The concentrations of fibronectin were tested by electrophoresis.RESULTS The fibronectin levels tended to increase with prolongation of culture time. There was a sharp increase after 72h in 10 or 15 LPS treated group. The peak level of fibronectin was above 20mg/L. However, cell proliferation was inhibited during the course. Cell number of untreated control group (4.6±0.1×106) was about three-fold that of 20 LPS treated group (1.6±0.2×106) at 120h.CONCLUSION Hepatocytes have a potent ability to produce fibronectin stimulated by endotoxin, suggesting that hepatocytes might participate in the process of liver fibrosis.展开更多
Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions wit...Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this reactive glycoprotein plays in the progression of injury but also for the insight further studies could provide towards the development of novel therapies for alcoholic liver disease.展开更多
文摘Fibronectin glomerulopathy is a rare autosomal dominant inherited glomerular disease associated with massive deposition of fibronectin.We recently diagnosed fibronectin glomerulopathy in a 29-year-old woman presenting nephrotic syndrome.Genetic analysis of fibronectin 1 gene showed heterozygosity for the Y973C mutation.However,this mutation was not found in her parents.She had stable renal function but persistent nephrotic proteinuria after one-year follow-up.
基金Project (2010DFA32270) supported by the Ministry of Science and Technology of China (International Science & Technology Cooperation Program of China) Project (51102090) supported by the National Natural Science Foundation of ChinaProject (NCET-12-0170) supported by the Program for New Century Excellent Talents in University of China
文摘An understanding of osteoblast adhesion and proliferation on biomaterials is crucial to optimizing the surfaces of artificial implants used in clinical practice. Polished, anodic oxidation （AO） and micro-arc oxidation （MAO） treated titanium （Ti） plates were used as model surfaces to study the adhesion of MG-63 cells. Cells were monitored for 0.5 and 4 h; faster adhesion and spreading of MG-63 ceils were observed on the AO and MAO modified samples. Stimulated secretion of fibronectin （FN） influenced the adhesion rates. In addition, AO and MAO modified surfaces promoted cell proliferation through apparent up-regulation of FN and integrin a5 transcription via outside-in signaling. This strongly suggests that FN secretion by osteoblasts plays an essential role in enhanced cell adhesion, spreading and proliferation on these modified Ti surfaces.
基金supported by Cure Alzheimer’s Fund (to RET and SHC)JPB Foundation (to RET),and R56AG072054 (to SHC)。
文摘Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.
基金supported in part by Canadian Institutes of Health Research(MOP 119540),National Natural Science Foundation of China-Canadian Institutes of Health Research(China-Canada Joint Health Research Initiative Program),Heart and Stroke Foundation of Canada(Ontario)supported by equipment Funds from St.Michael's Hospital,Canadian Blood Services,and Canada Foundation for Innovation
文摘Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.
基金supported by the National Natural Science Foundation of China,Nos.81601961(to KWY),81672242(to YW)the Key Construction Projects of Shanghai Health and Family Planning on Weak Discipline,China,No.2015ZB0401(to YW)
文摘Many studies have shown that fibronectin type III domain-containing protein 5(FDNC5) and brain-derived neurotrophic factor(BDNF) play vital roles in plasticity after brain injury. An enriched environment refers to an environment that provides animals with multi-sensory stimulation and movement opportunities. An enriched environment has been shown to promote the regeneration of nerve cells, synapses, and blood vessels in the animal brain after cerebral ischemia;however, the exact mechanisms have not been clarified. This study aimed to determine whether an enriched environment could improve neurobehavioral functions after the experimental inducement of cerebral ischemia and whether neurobehavioral outcomes were associated with the expression of FDNC5 and BDNF. This study established ischemic mouse models using permanent middle cerebral artery occlusion(pMCAO) on the left side. On postoperative day 1, the mice were randomly assigned to either enriched environment or standard housing condition groups. Mice in the standard housing condition group were housed and fed under standard conditions. Mice in the enriched environment group were housed in a large cage, containing various toys, and fed with a standard diet. Sham-operated mice received the same procedure, but without artery occlusion, and were housed and fed under standard conditions. On postoperative days 7 and 14, a beam-walking test was used to assess coordination, balance, and spatial learning. On postoperative days 16–20, a Morris water maze test was used to assess spatial learning and memory. On postoperative day 15, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex were analyzed by western blot assay. The results showed that compared with the standard housing condition group, the motor balance and coordination functions(based on beam-walking test scores 7 and 14 days after operation), spatial learning abilities(based on the spatial learning scores from the Morris water maze test 16–19 days after operation), and memory abilities(based on the memory scores of the Morris water maze test 20 days after operation) of the enriched environment group improved significantly. In addition, the expression levels of FDNC5 and BDNF proteins in the ipsilateral cerebral cortex increased in the enriched environment group compared with those in the standard housing condition group. Furthermore, the Pearson correlation coefficient showed that neurobehavioral functions were positively associated with the expression levels of FDNC5 and BDNF(r = 0.587 and r = 0.840, respectively). These findings suggest that an enriched environment upregulates FDNC5 protein expression in the ipsilateral cerebral cortex after cerebral ischemia, which then activates BDNF protein expression, improving neurological function. BDNF protein expression was positively correlated with improved neurological function. The experimental protocols were approved by the Institutional Animal Care and Use Committee of Fudan University, China(approval Nos. 20160858 A232, 20160860 A234) on February 24, 2016.
文摘AIM To investigate the adjusting effects of the Yanggan Jieyu (YGJY, nourishing the liver and alleviate mental depression) decoction on the plasma concentration of fibronectin (FN), fibronectin receptor (FNR), tumor necrosis factor alpha (TNF α) and the activity of interleukin 1 (IL 1) in patients with cirrhosis. METHODS Thirty four cases of cirrhosis (in decompensation) were divided into YGJY decotion treated group and control group treated by routine method. FN, FNR and TNF α were measured with ELESA and expressed as mg/L (FN, FNR) and ng/L (TNF α), and IL 1 was measured by mice thymocyte proliferation using β scintillation counter and expressed as cpm. RESULTS In YGJY decoction treated group, before treatment, FN was 247 9±97 2, FNR 5 6±2 7, TNF α 83 9±7 1 and IL 1 was 2760 8±813 6, and after treatment. FN was 298 3±93 2 ( P <0 01), FNR 4 3±2 3 ( P <0 05, TNF α 93 6±12 0 ( P <0 05) and IL 1 was 1922 3±847 0 ( P <0 05). The FN and TNF α plasma level after treatment increased remarkably, while FNR and IL 1 decreased obviously. In the control group before treatment, FN was 248 8±101 9, FNR 5 5±1 9, TNF α 126 1±48 1 and IL 1 was 2540 6±603 2, and after treatment was 241 6±77 1 ( P >0 05), FNR 5 4±1 2 ( P >0 05), TNF α 100 6±15 5 ( P >0 05) and IL 1 was 2360 6±860 0 ( P >0 05), the plasma levels of FN, TNF α, FNR and IL 1 did not change signifiantly. CONCLUSION YGJY decoction could prevent the process of the hepatic fibrosis by readjusting the plasma levels of FN, FNR, TNF α and IL 1 mediating acivities in cirrhosis, which is of clinical significance.
基金This is a part of the project supported by Natural Science Foundation of Guangdong Province,China.
文摘Objective To investigate the expression and change of the β3 integrin subunit and fibronectin in normal human oviductal tissue during various phases of the menstrual cycle and tubal ectopic pregnant tissueMethods Samples of normal ( n=29 ) and pregnant fallopian tube ( n=22 ) tissues were obtained from women who had normal cycle and history of normal pregnancy. Normal oviductal tissue samples were divided into 4 groups based on their menstrual cycle. Both expression and distribution of the β3 subunit and fibronectin were determined with the immunohistochemical method and the image analysis.Results The β3 subunit was expressed in the cytoplasm of ciliated cells. The expression level of the β3 subunit was higher after ovulation than that before ovulation in isthmus epithelium (P<0.001), and declined significantly after ovulation in ampullae epithelium (P<0.001). In umbrella epithelium within 4 days after ovulation, the expression level of the β3 subunit was observed at rather higher level among other phases (P <0.001). The ciliated and secretory cells of the epithelium except for where the pregnancy occurred in tubal pregnancy expressed the β3 subunit, and no significant relationship was found between the normal tubal tissue of the secretory phase and tubal ectopic pregnant tissue (P>0.05). Fibronectin was expressed in the basement membrane of human oviductal epithelium and matrix. The expression level of fibronectin was higher in the hyperplastic phase than that in the secretory one (P<0.001). And it was lower in normal tubal tissue of the secretory phase than that in tubal ectopic pregnant tissue (P<0.001).Conclusion Theβ3 integrin subunit was expressed in the ciliated cells of human oviductal epithelium, and fibronectin was expressed in the basement membrane of human oviductal epithelium and matrix. Their expression and change in oviductal tissue is based on different phases of menstrual cycle. The β3 subunit could not related to the occurrence of tubal ectopic pregnancy. Fibronectin could be the potential molecular basis for the tubal ectopic pregnancy.
基金National Natural Science Foundation of China (No.30772379)Education Department Project of Hunan Province, China(No.04A049)
文摘AIM: To determine the effects of a low dose latrunculin (LAT)-A on dexamethasone (Dex)-induced upregulation of extracellular matrix proteins fibronectin (FN) in cultured human trabecular meshwork (HTM) cells. METHODS: HTM cells were cultured to confluent and incubated with 0.4 mu mol/L Dex and/or 0.05 mu mol/L LAT-A. FN expression in HTM cells was evaluated by Western blot and immunofluorescence microscopy. RESULTS: Dex up-regulated FN production in HTM cells, failed to do so when co-incubated with LAT-A. LAT-A decreased production of FN in cultured HTM cells. CONCLUSION: This study indicated that LAT-A may modulate the expression of fibronectin in trabecular meshwork to achieve treatment for steroids and other types of glaucoma. It has an important prospect as an intraocular pressure-lowering drug.
文摘AIM To investigate the effect of endotoxin on liver fibrosis and further define the role of hepatocytes in production of fibronectin in primary liver cell culture by endotoxin.METHODS After isolation and seeding of hepatocytes, the obtained cells were added to various doses (0, 5, 10, 15 and 20mg/L) of LPS treated culture media. The cells were collected and counted at various periods (0, 12, 24, 48, 72, 96, 120h). The concentrations of fibronectin were tested by electrophoresis.RESULTS The fibronectin levels tended to increase with prolongation of culture time. There was a sharp increase after 72h in 10 or 15 LPS treated group. The peak level of fibronectin was above 20mg/L. However, cell proliferation was inhibited during the course. Cell number of untreated control group (4.6±0.1×106) was about three-fold that of 20 LPS treated group (1.6±0.2×106) at 120h.CONCLUSION Hepatocytes have a potent ability to produce fibronectin stimulated by endotoxin, suggesting that hepatocytes might participate in the process of liver fibrosis.
基金Supported by The National Institute on Alcohol Abuse and Al-coholism and the US Department of Veterans Affairs
文摘Fibronectins are adhesive glycoproteins that can be found in tissue matrices and circulating in various fluids of the body. The variable composition of fibronectin molecules facilitates a diversity of interactions with cell surface receptors that suggest a role for these proteins beyond the structural considerations of the extracellular matrix. These interactions implicate fibronectin in the regulation of mechanisms that also determine cell behavior and activity. The two major forms, plasma fibronectin (pFn) and cellular fibronectin (cFn), exist as balanced amounts under normal physiological conditions. However, during injury and/or disease, tissue and circulating levels of cFn become disproportionately elevated. The accumulating cFn, in addition to being a consequence of prolonged tissue damage, may in factstimulate cellular events that promote further damage. In this review, we summarize what is known regarding such interactions between fibronectin and cells that may influence the biological response to injury. We elaborate on the effects of cFn in the liver, specifically under a condition of chronic alcohol-induced injury. Studies have revealed that chronic alcohol consumption stimulates excess production of cFn by sinusoidal endothelial cells and hepatic stellate cells while impairing its clearance by other cell types resulting in the build up of this glycoprotein throughout the liver and its consequent increased availability to influence cellular activity that could promote the development of alcoholic liver disease. We describe recent findings by our laboratory that support a plausible role for cFn in the promotion of liver injury under a condition of chronic alcohol abuse and the implications of cFn stimulation on the pathogenesis of alcoholic liver disease. These findings suggest an effect of cFn in regulating cell behavior in the alcohol-injured liver that is worth further characterizing not only to gain a more comprehensive understanding of the role this reactive glycoprotein plays in the progression of injury but also for the insight further studies could provide towards the development of novel therapies for alcoholic liver disease.
