Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix （ECM）. Versican, like other members of its family, has unique N- and C-term...Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix （ECM）. Versican, like other members of its family, has unique N- and C-terminal globular regions, each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin by outlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican by virtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type Ⅰ collagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P- and L-selectins, and chemokines. Versican also binds to the cell surface proteins CD44, integrin β1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1. These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processes are discussed.展开更多
AIM: To investigate diffusion in mammalian cell culture by gel entrapment within hollow fibers. METHODS: Freshly isolated rat hepatocytes or human oral epidermoid carcinoma (KB) cells were entrapped in type I collagen...AIM: To investigate diffusion in mammalian cell culture by gel entrapment within hollow fibers. METHODS: Freshly isolated rat hepatocytes or human oral epidermoid carcinoma (KB) cells were entrapped in type I collagen solutions and statically cultured inside microporous and ultrafiltration hollow fibers. During the culture time collagen gel contraction, cell viability and specific function were assessed. Effective diffusion coefficients of glucose in cell-matrix gels were determined by lag time analysis in a diffusion cell. RESULTS: Significant gel contractions occurred in the collagen gels by entrapment of either viable hepatocytes or KB cells. And the gel contraction caused a significant reduction on effective diffusion coefficient of glucose. The cell viability assay of both hepatocytes and KB cells statically cultured in hollow fibers by collagen entrapment further confirmed the existence of the inhibited mass transfer by diffusion. Urea was secreted about 50% more by hepatocytes entrapped in hollow fibers with pore size of 0.1 μm than that in hollow fibers with MWCO of 100 ku. CONCLUSION: Cell-matrix gel and membrane pore size are the two factors relevant to the limited mass transfer by diffusion in such gel entrapment of mammalian cell culture.展开更多
AIM： To investigate the anti-fibrosis effect of the tissue transglutarninase （tTG） specific inhibitor cystarnine on liver fibrosis. METHODS： Sixty-eight male Sprague Dawley rats were divided into three groups： no...AIM： To investigate the anti-fibrosis effect of the tissue transglutarninase （tTG） specific inhibitor cystarnine on liver fibrosis. METHODS： Sixty-eight male Sprague Dawley rats were divided into three groups： normal control, liver fibrosis control and cystamine-treated group. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride （CCl4）, and Cystarnine was administrated by intraperitoneal injection starting 2 d before the first administration of CCl4. Animals in each group were further divided into 2 subgroups according to two time points of 4 wk and 8 wk after treatment. Hepatic function, pathological evaluation （semi-quantitative scoring system, SSS） and liver hydroxyproline （Hyp） content were examined. Real-time PCR was used to detect the expression of tTG, smooth muscle alpha actin （α-SMA）, tissue inhibitor of metalloproteinase 1 （TIMP-1） and collagen-1 mRNA. The expressions of tTG and α-SMA protein were detected by Western Blotting. RESULTS： Eight weeks after treatment, the SSS score of liver was significantly less in the cystamine group than that in the fibrosis control group （P 〈 0.01）. The levels of alanine arninotransferase （ALT） and total bile acid （TBA） at the 4 wk and 8 wk time points were decreased in the cystamine group compared with those in fibrosis controls （P 〈 0.01）. Liver hydroxyproline content at the 4 wk and 8 wk time points showed a substantial reduction in the cystamine group compared to fibrosis controls （P 〈 0.01）. The expression of tTG, α-SMA, collagen-1, TIMP-1 mRNA and tTG, as well as α-SMA protein was downregulated in the cystamine group compared to fibrosis controls. CONCLUSION： Cystamine can ameliorate CCl4 induced liver fibrosis and protect hepatic function. The possible mechanism is related to the reduced synthesis of the extracellular matrix （ECM） caused by the inhibition of hepatic stellate cell activation and decreased expression of TIMP-1.展开更多
Liver fibrosis is an important pathological precondition for hepatocellular carcinoma.The degree of hepatic fibrosis is positively correlated with liver cancer.Liver fibrosis is a series of pathological and physiologi...Liver fibrosis is an important pathological precondition for hepatocellular carcinoma.The degree of hepatic fibrosis is positively correlated with liver cancer.Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury,which finally leads to extracellular matrix and collagen deposition.The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens.The risk of severe liver fibrosis finally progressing to liver carcinoma is＆gt;50%.It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis.However,this method has some limitations,such as the potential for pain,sampling variability,and low patient acceptance.Furthermore,the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial.An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice,mostly in cases of viral hepatitis,resulting in a significantly decreased need for liver biopsy.In fact,the noninvasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers,ultrasound imaging,and magnetic resonance imaging quantification techniques.A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient.Serum biomarkers have the advantages of high applicability（〉95%）and good reproducibility.However,their results can be influenced by different patient conditions because none of these markers are liver-specific.The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages,and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis.This article aims to describe the recent progress in the development of non-invasive assessment methods for the staging of liver fibrosis,with a special emphasize on computer-aided quantitative and deep learning methods.展开更多
Objective：Hyperglycemia stimulates secretion of transforming growth factor-βl （TGF-βl） in cultured glomerular mesangial cells, thereby increases production of extracellular matrix （ECM）. We examined the effect ...Objective：Hyperglycemia stimulates secretion of transforming growth factor-βl （TGF-βl） in cultured glomerular mesangial cells, thereby increases production of extracellular matrix （ECM）. We examined the effect of antisense mRNA for Smad2 on high glucose-induced ECM production in rat mesangial cells. Methods..A mammalian expression vector, pES2a, which expresses antisense Smad2 mRNA and green fluorescent protein （EGFP）, was transfected into mesangial cells. Following incubation in high glucose medium, EGFP expression and Smad2 mRNA level were determined by fluorescence microscopy and PCR, respectively. Secreted fibronectin and type IV collagen were assessed by enzyme-linked immunosorbent assay. Results ：Within 48 h of incubation in high glucose medium, Smad2 mRNA level significantly increased by 1.6 fold in association with increases in prodtaction of both fibronectin （from [45.86±2.73] to [84.19±6.81] ng/ml） and type IV collagen （from [16. 28±0. 90] to [55.27±4.75] ng/ml） in nontransfected cells （P〈0.05）. In pES2a-transfected cells, the high glucose-induced increase in Smad2 mRNA was abrogated completely, in parallel with significant suppression of the high glucose-indtmed increase in fibronectinproduction （[54.44±4.99] ng/ml） and type Ⅳ collagen （[20.96±2.47] ng/ml）. An empty vector was without effects. Coneluslon：These findings demonstrate that Smad2 plays a critical role in mediating high glucose-stimulated ECM production in mesangial cells, indicating that inhibition of Smad2 activity by antisense Smad2 mRNA may be an effective means to attenuate glomerular matrix accumulation in diabetic nephropathy.展开更多
OBJECTIVE To investigate the significance and relationship between matrix metalloproteinase 9 （MMP-9） and infiltration of macrophages in the process of invasion and metastasis in oral squamous cell carcinoma （OSCC...OBJECTIVE To investigate the significance and relationship between matrix metalloproteinase 9 （MMP-9） and infiltration of macrophages in the process of invasion and metastasis in oral squamous cell carcinoma （OSCC）. METHODS The immunohistochemical SABC method was used to detect the expression of MMP-9 and CD68 （for labeling macrophages） in 42 cases of OSCC and in 10 normal tissues. RESULTS The expression of MMP-9 and macrophage counts in the OSCC cases were significantly higher compared to normal tissues （P〈0.05）. The expression of MMP-9 and macrophage counts were related to lymphnode metastasis and the TNM stage （P〈0.05）, showing that there was a positive correlation among these parameters （y = 0.443, ,0〈0.01）. CONCLUSION Both MMP-9 and macrophages may play an important role in the process of invasion and metastasis in OSCC, and this cellular activity may relate to the macrophages which affect the tumor cells and upregulate the expression of MMP-9.展开更多
Integrin-mediated adhesions play critical roles in diverse cell functions. Integrins offers a platform on which mechanical stimuli, cytoskeletal organization, biochemical signals can concentrate. Mechanical stimuli tr...Integrin-mediated adhesions play critical roles in diverse cell functions. Integrins offers a platform on which mechanical stimuli, cytoskeletal organization, biochemical signals can concentrate. Mechanical stimuli transmitted by integrins influence the cytoskeleton, in turn, the cytoskeleton influences cell adhesion via integrins, then cell adhesion results in a series of signal transduction cascades. In skeleton, integrins also have a key role for bone resoption by osteoclasts and reformation by osteoblasts. In present review, the proteins involved in integrin signal transduction and integrin signal transduction pathways were discussed, mainly on the basic mechanisms of integrin signaling and the roles of integrins in bone signal transduction, which may give insight into new therapeutic agents to all kinds of skeletal diseases and new strategies for bone tissue engineering.展开更多
MMPs and their natural tissue inhibitors TIMPs are crucial in coordinated breakdown and remodel- ing of the extracellular matrix (ECM) in physiological and pathological situations. Placentation is a key event of pregn...MMPs and their natural tissue inhibitors TIMPs are crucial in coordinated breakdown and remodel- ing of the extracellular matrix (ECM) in physiological and pathological situations. Placentation is a key event of pregnancy in which MMPs/TIMPs system plays important roles in regulating the extravillus cytotrophoblast (EVTs) invasion. This paper focuses on expression patterns and regulatory mechanisms of MMPs/TIMPs family members during the process of placentation. Their implications in curing pregnancy-related diseases are also discussed.展开更多
The authors prove that an operator with the cellular indecomposable property has no singular points in the semi-Fredholm domain, by applying the 4 x 4 matrix model of semi-Fredholm operators due to Fang in 2004. This ...The authors prove that an operator with the cellular indecomposable property has no singular points in the semi-Fredholm domain, by applying the 4 x 4 matrix model of semi-Fredholm operators due to Fang in 2004. This result fills a gap in the result of Olin and Thomson in 1984.展开更多
文摘Versican belongs to the family of the large aggregating chondroitin sulfate proteoglycans located primarily within the extracellular matrix （ECM）. Versican, like other members of its family, has unique N- and C-terminal globular regions, each with multiple motifs. A large glycosaminoglycan-binding region lies between them. This review will begin by outlining these structures, in the context of ECM proteoglycans. The diverse binding partners afforded to versican by virtue of its modular design will then be examined. These include ECM components, such as hyaluronan, type Ⅰ collagen, tenascin-R, fibulin-1, and -2, fibrillin-1, fibronectin, P- and L-selectins, and chemokines. Versican also binds to the cell surface proteins CD44, integrin β1, epidermal growth factor receptor, and P-selectin glycoprotein ligand-1. These multiple interactors play important roles in cell behaviour, and the roles of versican in modulating such processes are discussed.
基金Supported by the National Natural Science Foundation of China,No.90209053Zhejiang Scientific Project, No. 2003C31042
文摘AIM: To investigate diffusion in mammalian cell culture by gel entrapment within hollow fibers. METHODS: Freshly isolated rat hepatocytes or human oral epidermoid carcinoma (KB) cells were entrapped in type I collagen solutions and statically cultured inside microporous and ultrafiltration hollow fibers. During the culture time collagen gel contraction, cell viability and specific function were assessed. Effective diffusion coefficients of glucose in cell-matrix gels were determined by lag time analysis in a diffusion cell. RESULTS: Significant gel contractions occurred in the collagen gels by entrapment of either viable hepatocytes or KB cells. And the gel contraction caused a significant reduction on effective diffusion coefficient of glucose. The cell viability assay of both hepatocytes and KB cells statically cultured in hollow fibers by collagen entrapment further confirmed the existence of the inhibited mass transfer by diffusion. Urea was secreted about 50% more by hepatocytes entrapped in hollow fibers with pore size of 0.1 μm than that in hollow fibers with MWCO of 100 ku. CONCLUSION: Cell-matrix gel and membrane pore size are the two factors relevant to the limited mass transfer by diffusion in such gel entrapment of mammalian cell culture.
基金Supported by National Natural Science Foundation of China,No. 30571825
文摘AIM： To investigate the anti-fibrosis effect of the tissue transglutarninase （tTG） specific inhibitor cystarnine on liver fibrosis. METHODS： Sixty-eight male Sprague Dawley rats were divided into three groups： normal control, liver fibrosis control and cystamine-treated group. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride （CCl4）, and Cystarnine was administrated by intraperitoneal injection starting 2 d before the first administration of CCl4. Animals in each group were further divided into 2 subgroups according to two time points of 4 wk and 8 wk after treatment. Hepatic function, pathological evaluation （semi-quantitative scoring system, SSS） and liver hydroxyproline （Hyp） content were examined. Real-time PCR was used to detect the expression of tTG, smooth muscle alpha actin （α-SMA）, tissue inhibitor of metalloproteinase 1 （TIMP-1） and collagen-1 mRNA. The expressions of tTG and α-SMA protein were detected by Western Blotting. RESULTS： Eight weeks after treatment, the SSS score of liver was significantly less in the cystamine group than that in the fibrosis control group （P 〈 0.01）. The levels of alanine arninotransferase （ALT） and total bile acid （TBA） at the 4 wk and 8 wk time points were decreased in the cystamine group compared with those in fibrosis controls （P 〈 0.01）. Liver hydroxyproline content at the 4 wk and 8 wk time points showed a substantial reduction in the cystamine group compared to fibrosis controls （P 〈 0.01）. The expression of tTG, α-SMA, collagen-1, TIMP-1 mRNA and tTG, as well as α-SMA protein was downregulated in the cystamine group compared to fibrosis controls. CONCLUSION： Cystamine can ameliorate CCl4 induced liver fibrosis and protect hepatic function. The possible mechanism is related to the reduced synthesis of the extracellular matrix （ECM） caused by the inhibition of hepatic stellate cell activation and decreased expression of TIMP-1.
文摘Liver fibrosis is an important pathological precondition for hepatocellular carcinoma.The degree of hepatic fibrosis is positively correlated with liver cancer.Liver fibrosis is a series of pathological and physiological process related to liver cell necrosis and degeneration after chronic liver injury,which finally leads to extracellular matrix and collagen deposition.The early detection and precise staging of fibrosis and cirrhosis are very important for early diagnosis and timely initiation of appropriate therapeutic regimens.The risk of severe liver fibrosis finally progressing to liver carcinoma is＆gt;50%.It is known that biopsy is the gold standard for the diagnosis and staging of liver fibrosis.However,this method has some limitations,such as the potential for pain,sampling variability,and low patient acceptance.Furthermore,the necessity of obtaining a tissue diagnosis of liver fibrosis still remains controversial.An increasing number of reliable non-invasive approaches are now available that are widely applied in clinical practice,mostly in cases of viral hepatitis,resulting in a significantly decreased need for liver biopsy.In fact,the noninvasive detection and evaluation of liver cirrhosis now has good accuracy due to current serum markers,ultrasound imaging,and magnetic resonance imaging quantification techniques.A prominent advantage of the non-invasive detection and assessment of liver fibrosis is that liver fibrosis can be monitored repeatedly and easily in the same patient.Serum biomarkers have the advantages of high applicability（〉95%）and good reproducibility.However,their results can be influenced by different patient conditions because none of these markers are liver-specific.The most promising techniques appear to be transient elastography and magnetic resonance elastography because they provide reliable results for the detection of fibrosis in the advanced stages,and future developments promise to increase the reliability and accuracy of the staging of hepatic fibrosis.This article aims to describe the recent progress in the development of non-invasive assessment methods for the staging of liver fibrosis,with a special emphasize on computer-aided quantitative and deep learning methods.
文摘Objective：Hyperglycemia stimulates secretion of transforming growth factor-βl （TGF-βl） in cultured glomerular mesangial cells, thereby increases production of extracellular matrix （ECM）. We examined the effect of antisense mRNA for Smad2 on high glucose-induced ECM production in rat mesangial cells. Methods..A mammalian expression vector, pES2a, which expresses antisense Smad2 mRNA and green fluorescent protein （EGFP）, was transfected into mesangial cells. Following incubation in high glucose medium, EGFP expression and Smad2 mRNA level were determined by fluorescence microscopy and PCR, respectively. Secreted fibronectin and type IV collagen were assessed by enzyme-linked immunosorbent assay. Results ：Within 48 h of incubation in high glucose medium, Smad2 mRNA level significantly increased by 1.6 fold in association with increases in prodtaction of both fibronectin （from [45.86±2.73] to [84.19±6.81] ng/ml） and type IV collagen （from [16. 28±0. 90] to [55.27±4.75] ng/ml） in nontransfected cells （P〈0.05）. In pES2a-transfected cells, the high glucose-induced increase in Smad2 mRNA was abrogated completely, in parallel with significant suppression of the high glucose-indtmed increase in fibronectinproduction （[54.44±4.99] ng/ml） and type Ⅳ collagen （[20.96±2.47] ng/ml）. An empty vector was without effects. Coneluslon：These findings demonstrate that Smad2 plays a critical role in mediating high glucose-stimulated ECM production in mesangial cells, indicating that inhibition of Smad2 activity by antisense Smad2 mRNA may be an effective means to attenuate glomerular matrix accumulation in diabetic nephropathy.
基金the National Natural Science Foundation of China (No. 30660200)the Provincial Governor’s Special Fund of Guizhou Province, China (No. 005-160).
文摘OBJECTIVE To investigate the significance and relationship between matrix metalloproteinase 9 （MMP-9） and infiltration of macrophages in the process of invasion and metastasis in oral squamous cell carcinoma （OSCC）. METHODS The immunohistochemical SABC method was used to detect the expression of MMP-9 and CD68 （for labeling macrophages） in 42 cases of OSCC and in 10 normal tissues. RESULTS The expression of MMP-9 and macrophage counts in the OSCC cases were significantly higher compared to normal tissues （P〈0.05）. The expression of MMP-9 and macrophage counts were related to lymphnode metastasis and the TNM stage （P〈0.05）, showing that there was a positive correlation among these parameters （y = 0.443, ,0〈0.01）. CONCLUSION Both MMP-9 and macrophages may play an important role in the process of invasion and metastasis in OSCC, and this cellular activity may relate to the macrophages which affect the tumor cells and upregulate the expression of MMP-9.
文摘Integrin-mediated adhesions play critical roles in diverse cell functions. Integrins offers a platform on which mechanical stimuli, cytoskeletal organization, biochemical signals can concentrate. Mechanical stimuli transmitted by integrins influence the cytoskeleton, in turn, the cytoskeleton influences cell adhesion via integrins, then cell adhesion results in a series of signal transduction cascades. In skeleton, integrins also have a key role for bone resoption by osteoclasts and reformation by osteoblasts. In present review, the proteins involved in integrin signal transduction and integrin signal transduction pathways were discussed, mainly on the basic mechanisms of integrin signaling and the roles of integrins in bone signal transduction, which may give insight into new therapeutic agents to all kinds of skeletal diseases and new strategies for bone tissue engineering.
基金supported by the National Natural Science Foundation of China(Grant No,30440043)Basis Research Foundations of Tsinghua University(Grant No.Jc2003015).
基金supported by the Special Funds for Major State Basic Research Project(Grant No.G1999055903)Funds from CAS(Grant No.KSCX2-SW-322)trom NSFC(Grant No.30170112).
文摘MMPs and their natural tissue inhibitors TIMPs are crucial in coordinated breakdown and remodel- ing of the extracellular matrix (ECM) in physiological and pathological situations. Placentation is a key event of pregnancy in which MMPs/TIMPs system plays important roles in regulating the extravillus cytotrophoblast (EVTs) invasion. This paper focuses on expression patterns and regulatory mechanisms of MMPs/TIMPs family members during the process of placentation. Their implications in curing pregnancy-related diseases are also discussed.
基金Project supported by the National Natural Science Foundation of China(No.11101312)the National Science Foundation(No.0801174)
文摘The authors prove that an operator with the cellular indecomposable property has no singular points in the semi-Fredholm domain, by applying the 4 x 4 matrix model of semi-Fredholm operators due to Fang in 2004. This result fills a gap in the result of Olin and Thomson in 1984.
