AIM： To study the effect of IL-10 on the expression of growth factors - transforming growth factor-β1 （TGF-β1）, epidermal growth factor （EGF）, hepatocyte growth factor （HGF）and platelet-derived growth factor ...AIM： To study the effect of IL-10 on the expression of growth factors - transforming growth factor-β1 （TGF-β1）, epidermal growth factor （EGF）, hepatocyte growth factor （HGF）and platelet-derived growth factor （PDGF） of hepatic stellate cells （HSCs） of hepatic fibrosis rat and the anti-fibrogenic role of exogenous IL-10. METHODS： Hepatic fibrosis was induced by CCI4 administration intra-peritoneally. Sixty clean male Sprague-Dawley （SD） rats were randomly divided into three groups： normal control group （GN, 8 rats）, hepatic fibrosis model group （GC, 28 rats） and IL-10 treated group （GI, 24 rats）. At the beginning of the 7^th and 11^th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through a portal vein catheter and the suspension obtained from the liver was spun by centrifugation with 11% Nycodenz density gradient to isolate HSCs. Histological examination was used to determine the degree of hepatic fibrosis. RT-PCR was employed to analyze mRNA expression from freshly isolated cells. Immunocytochemistry was performed to detect protein expression in primary cultured HSCs. RESULTS： Rat hepatic fibrosis was developed with the increase of injection frequency of CCl4, and HSCs were successfully isolated. At the 7^th and 11^th wk, TGF-β1, EGF, and HGF mRNA in GC increased obviously compared with GN （P = 0.001/0.042, 0.001/0.001, 0.001/0.001） and GI （P= 0.001/0.007, 0.002/0.001, 0.001/0.001）. For TGF-β1, no difference was observed between GI and GN. For EGF, mRNA level in GI increased compared with GN during the 7^th wk （P= 0.005） and 11^th wk （P= 0.049）. For HGF, mRNA level in GI decreased compared with GN at the 7^th wk （P = 0.001） and 11^th wk （P= 0.021）. Between these two time points, TGF-β1 expression at the 7^th wk was higher than that of the 11^th wk （P = 0.049）, but for EGF, the former was lower than the latter （P = 0.022）. As for PDGF mRNA, there was no significant difference between thesegroups, but difference seemed to exist in protein levels. Results by immunocytochemistry of TGF-β1 and EGF were paralleled with the above findings. CONCLUSION： The expression of TGF-β1, EGF and HGF increased in HSC of hepatic fibrosis rat and decreased after treatment with IL-10. IL-10 plays an anti-fibrogenic role by suppressing growth factors expression.展开更多
There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part ...There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part I, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide （GLP）-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.展开更多
AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN).
Objective To eoplore ulhether or not growth factors are involved in the restenosis afterangioplasty .Methods A rabbit model of atherosclerosis was established with cholesterol feeding after iliacartery injury made wit...Objective To eoplore ulhether or not growth factors are involved in the restenosis afterangioplasty .Methods A rabbit model of atherosclerosis was established with cholesterol feeding after iliacartery injury made with an inflated balloon catheter. Then balloon angioplasty was made. Expression oftransforming growth factor /β1(TGF-β1), epidermal growth factor receptor (EGFR), and basic fibroblast growthfactor (bFGF) mRNA was observed in rabbit iliac artery before and after balloon angioplasty with hybridization ofNorthern blot and reverse transcription polymerase chain reaction. Results Expression of TGF- β1. EGFR andbFGF mRNA in rabbit iliac artery was significantly increased 1 week and 2 weeks after angioplasty in comparisonwith that before angioplasty, Conclusion TGF-β1, EGFR and bFGF may be involved in the restenosis afterangioplasts.展开更多
目的:探讨靶向结缔组织生长因子(CTGF)的锤头核酶抑制TGF-β1作用下人肝星状细胞(HSC)Ⅰ型胶原(Col I)合成及其细胞周期进程的作用.方法:构建含有人CTGF锤头核酶cDNA序列的重组质粒pTriCTGF-Rz.将空质粒pTriEx2和重组质粒pTriCTGF-Rz分...目的:探讨靶向结缔组织生长因子(CTGF)的锤头核酶抑制TGF-β1作用下人肝星状细胞(HSC)Ⅰ型胶原(Col I)合成及其细胞周期进程的作用.方法:构建含有人CTGF锤头核酶cDNA序列的重组质粒pTriCTGF-Rz.将空质粒pTriEx2和重组质粒pTriCTGF-Rz分别转染人肝星状细胞系(LX-2)细胞.细胞分为4组:pTriEx2转染组,pTriEx2转染加TGF-β1组,pTriCTGF-Rz转染加TGF-β1组和pTriCTGF-Rz转染组.采用半定量RT-PCR测定LX-2细胞CTGF mRNA和Col I mRNA转录水平,采用ELISA和流式细胞仪分别用于LX-2细胞Col I分泌功能和LX-2细胞周期进程的检测.结果:TGF-β1可明显提高LX-2细胞CTGFmRNA和Col I mRNA的转录水平及分泌ColI蛋白功能(t=11.14,14.36,7.17,均P<0.01);p Tr i C T G F-R z转染L X-2细胞既能降低基础CTGF mRNA和Col I mRNA水平及Col I蛋白水平(t=2.86,3.06,2.97,均P<0.05),又能部分拮抗TGF-β1诱导LX-2细胞CTGF mRNA和Col I mRNA转录和Col I蛋白分泌的增加(t=2.99,3.09,3.02,均P<0.05).TGF-β1对LX-2细胞周期进程无影响.结论:CTGF是TGF-β1作用下人肝星状细胞合成Col I的下游介导者,TGF-β1对HSC周期进程无影响,靶向CTGF有可能成为肝纤维化基因治疗的新靶点.展开更多
Objective: Irradiation may enhance migration and/or invasiveness of cancer cells in vitro and in vivo, the mechanism of which may be associated with epithelial-mesenchymal transition (EMT). The present study explored ...Objective: Irradiation may enhance migration and/or invasiveness of cancer cells in vitro and in vivo, the mechanism of which may be associated with epithelial-mesenchymal transition (EMT). The present study explored the mechanisms of EMT induced by irradiation in esophageal cancer cells. Methods: Human esophageal cancer cell line EC109 was treated with increased doses of irradiation (0 Gy, 20 Gy, 40 Gy and 60 Gy). Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by immunofluorescence assay or western blot. Secretion of transforming growth factor-β1 (TGF-β1) by cells was determined by enzyme-linked immunosorbent assay (ELISA), and the expressions of Smad2/3 and phosphorated Smad2 (p-Smad2) were also examined by Western blot. The mRNA expressions of BMP-4, a bone morphogenetic protein (BMP) ligand, and two secreted BMP antagonists (Chordin and Gremlin), were detected with reverse transcription-polymerase chain reaction (RT-PCR). Cell migratory capacity was evaluated. Results: Irradiation induced EMT in EC109 cells in a dose-dependent manner as evidenced by morphological changes, decreased expression of E-cadherin and increased expression of vimentin, and increased cell motility. The secretion of TGF-β1 and expression of p-Smad2 were gradually increased in an irradiation dose-dependent manner, but the Smad2/3 protein levels remained stable. The mRNA expression of BMP-4 was gradually down-regulated, but the expressions of Chordin and Gremlin were gradually up-regulated in cells treated with increased doses of irradiation. Conclusion: Irradiation can induce EMT in esophageal cancer cells in a dose-dependent manner, and the mechanism may be associated with activation of TGF-β and restriction of BMP signaling.展开更多
Evidence has accumulated to suggest an important role of ethanol and/or its metabolites in the pathogenesis of alcohol-related liver disease. In this review, the fibrogenic effects of ethanol and its metabolites on he...Evidence has accumulated to suggest an important role of ethanol and/or its metabolites in the pathogenesis of alcohol-related liver disease. In this review, the fibrogenic effects of ethanol and its metabolites on hepatic stellate cells (HSCs) are discussed. In brief, ethanol interferes with retinoid metabolism and its signaling, induces the release of fibrogenic cytokines such as transforming growth factor β-1 (TGFβ-1) from HSCs, up-regulates the gene expression of collagen I and enhances type I collagen protein production by HSCs. Ethanol further perpetuates an activated HSC phenotype through extracellular matrix remodeling. The underlying pathophysiologic mechanisms by which ethanol exerts these pro-fibrogenic effects on HSCs are reviewed.展开更多
基金Supported by Technology and Science Foundation of Fujian Province, No. 2003 D05
文摘AIM： To study the effect of IL-10 on the expression of growth factors - transforming growth factor-β1 （TGF-β1）, epidermal growth factor （EGF）, hepatocyte growth factor （HGF）and platelet-derived growth factor （PDGF） of hepatic stellate cells （HSCs） of hepatic fibrosis rat and the anti-fibrogenic role of exogenous IL-10. METHODS： Hepatic fibrosis was induced by CCI4 administration intra-peritoneally. Sixty clean male Sprague-Dawley （SD） rats were randomly divided into three groups： normal control group （GN, 8 rats）, hepatic fibrosis model group （GC, 28 rats） and IL-10 treated group （GI, 24 rats）. At the beginning of the 7^th and 11^th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through a portal vein catheter and the suspension obtained from the liver was spun by centrifugation with 11% Nycodenz density gradient to isolate HSCs. Histological examination was used to determine the degree of hepatic fibrosis. RT-PCR was employed to analyze mRNA expression from freshly isolated cells. Immunocytochemistry was performed to detect protein expression in primary cultured HSCs. RESULTS： Rat hepatic fibrosis was developed with the increase of injection frequency of CCl4, and HSCs were successfully isolated. At the 7^th and 11^th wk, TGF-β1, EGF, and HGF mRNA in GC increased obviously compared with GN （P = 0.001/0.042, 0.001/0.001, 0.001/0.001） and GI （P= 0.001/0.007, 0.002/0.001, 0.001/0.001）. For TGF-β1, no difference was observed between GI and GN. For EGF, mRNA level in GI increased compared with GN during the 7^th wk （P= 0.005） and 11^th wk （P= 0.049）. For HGF, mRNA level in GI decreased compared with GN at the 7^th wk （P = 0.001） and 11^th wk （P= 0.021）. Between these two time points, TGF-β1 expression at the 7^th wk was higher than that of the 11^th wk （P = 0.049）, but for EGF, the former was lower than the latter （P = 0.022）. As for PDGF mRNA, there was no significant difference between thesegroups, but difference seemed to exist in protein levels. Results by immunocytochemistry of TGF-β1 and EGF were paralleled with the above findings. CONCLUSION： The expression of TGF-β1, EGF and HGF increased in HSC of hepatic fibrosis rat and decreased after treatment with IL-10. IL-10 plays an anti-fibrogenic role by suppressing growth factors expression.
文摘There are various hormones and growth factors which may modify the intestinal absorption of nutrients, and which might thereby be useful in a therapeutic setting, such as in persons with short bowel syndrome. In part I, we focus first on insulin-like growth factors, epidermal and transferring growth factors, thyroid hormones and glucocorticosteroids. Part Ⅱ will detail the effects of glucagon-like peptide （GLP）-2 on intestinal absorption and adaptation, and the potential for an additive effect of GLP2 plus steroids.
基金Supported by Medical University of Gdansk Grants ST-43,ST-40 and ST-41 and Polpharma(Starogard Gdanski)
文摘AIM: To examine circulating growth factor concentrations in patients with acute pancreatitis (AP) and chronic pancreatitis (CP), and walled-off pancreatic necrosis (WOPN).
文摘Objective To eoplore ulhether or not growth factors are involved in the restenosis afterangioplasty .Methods A rabbit model of atherosclerosis was established with cholesterol feeding after iliacartery injury made with an inflated balloon catheter. Then balloon angioplasty was made. Expression oftransforming growth factor /β1(TGF-β1), epidermal growth factor receptor (EGFR), and basic fibroblast growthfactor (bFGF) mRNA was observed in rabbit iliac artery before and after balloon angioplasty with hybridization ofNorthern blot and reverse transcription polymerase chain reaction. Results Expression of TGF- β1. EGFR andbFGF mRNA in rabbit iliac artery was significantly increased 1 week and 2 weeks after angioplasty in comparisonwith that before angioplasty, Conclusion TGF-β1, EGFR and bFGF may be involved in the restenosis afterangioplasts.
文摘目的:探讨靶向结缔组织生长因子(CTGF)的锤头核酶抑制TGF-β1作用下人肝星状细胞(HSC)Ⅰ型胶原(Col I)合成及其细胞周期进程的作用.方法:构建含有人CTGF锤头核酶cDNA序列的重组质粒pTriCTGF-Rz.将空质粒pTriEx2和重组质粒pTriCTGF-Rz分别转染人肝星状细胞系(LX-2)细胞.细胞分为4组:pTriEx2转染组,pTriEx2转染加TGF-β1组,pTriCTGF-Rz转染加TGF-β1组和pTriCTGF-Rz转染组.采用半定量RT-PCR测定LX-2细胞CTGF mRNA和Col I mRNA转录水平,采用ELISA和流式细胞仪分别用于LX-2细胞Col I分泌功能和LX-2细胞周期进程的检测.结果:TGF-β1可明显提高LX-2细胞CTGFmRNA和Col I mRNA的转录水平及分泌ColI蛋白功能(t=11.14,14.36,7.17,均P<0.01);p Tr i C T G F-R z转染L X-2细胞既能降低基础CTGF mRNA和Col I mRNA水平及Col I蛋白水平(t=2.86,3.06,2.97,均P<0.05),又能部分拮抗TGF-β1诱导LX-2细胞CTGF mRNA和Col I mRNA转录和Col I蛋白分泌的增加(t=2.99,3.09,3.02,均P<0.05).TGF-β1对LX-2细胞周期进程无影响.结论:CTGF是TGF-β1作用下人肝星状细胞合成Col I的下游介导者,TGF-β1对HSC周期进程无影响,靶向CTGF有可能成为肝纤维化基因治疗的新靶点.
基金supported by a grant from the Huai'an City Science and Technology Support Program (Social Development) (No. HAS 2010010)
文摘Objective: Irradiation may enhance migration and/or invasiveness of cancer cells in vitro and in vivo, the mechanism of which may be associated with epithelial-mesenchymal transition (EMT). The present study explored the mechanisms of EMT induced by irradiation in esophageal cancer cells. Methods: Human esophageal cancer cell line EC109 was treated with increased doses of irradiation (0 Gy, 20 Gy, 40 Gy and 60 Gy). Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by immunofluorescence assay or western blot. Secretion of transforming growth factor-β1 (TGF-β1) by cells was determined by enzyme-linked immunosorbent assay (ELISA), and the expressions of Smad2/3 and phosphorated Smad2 (p-Smad2) were also examined by Western blot. The mRNA expressions of BMP-4, a bone morphogenetic protein (BMP) ligand, and two secreted BMP antagonists (Chordin and Gremlin), were detected with reverse transcription-polymerase chain reaction (RT-PCR). Cell migratory capacity was evaluated. Results: Irradiation induced EMT in EC109 cells in a dose-dependent manner as evidenced by morphological changes, decreased expression of E-cadherin and increased expression of vimentin, and increased cell motility. The secretion of TGF-β1 and expression of p-Smad2 were gradually increased in an irradiation dose-dependent manner, but the Smad2/3 protein levels remained stable. The mRNA expression of BMP-4 was gradually down-regulated, but the expressions of Chordin and Gremlin were gradually up-regulated in cells treated with increased doses of irradiation. Conclusion: Irradiation can induce EMT in esophageal cancer cells in a dose-dependent manner, and the mechanism may be associated with activation of TGF-β and restriction of BMP signaling.
文摘Evidence has accumulated to suggest an important role of ethanol and/or its metabolites in the pathogenesis of alcohol-related liver disease. In this review, the fibrogenic effects of ethanol and its metabolites on hepatic stellate cells (HSCs) are discussed. In brief, ethanol interferes with retinoid metabolism and its signaling, induces the release of fibrogenic cytokines such as transforming growth factor β-1 (TGFβ-1) from HSCs, up-regulates the gene expression of collagen I and enhances type I collagen protein production by HSCs. Ethanol further perpetuates an activated HSC phenotype through extracellular matrix remodeling. The underlying pathophysiologic mechanisms by which ethanol exerts these pro-fibrogenic effects on HSCs are reviewed.
