AIM: To elucidate the interaction between non- parenchymal cells, extracellular matrix and oval cells during the restituting process of liver injury induced by partial hepatectomy (PH). METHODS: We examined the lo...AIM: To elucidate the interaction between non- parenchymal cells, extracellular matrix and oval cells during the restituting process of liver injury induced by partial hepatectomy (PH). METHODS: We examined the localization of oval cells, non-parenchymal cells, and the extracellular matrix components using immunohistochemical and double immunofluorescent analysis during the proliferation and differentiation of oval cells in N-2- acetylaminofluorene (2-AAF)/PH rat model. RESULTS: By day 2 after PH, small oval cells began to proliferate around the portal area. Most of stellate cells and laminin were present along the hepatic sinusoids in the periportal area. Kupffer cells and fibronectin markedly increased in the whole hepatic Iobule. From day 4 to 9, oval cells spread further into hepatic parenchyma, closely associated with stellate cells, fibronectin and laminin. Kupffer cells admixed with oval cells by day 6 and then decreased in the periportal zone. From day 12 to 15, most of hepatic stellate cells (HSCs), laminin and fibronectin located around the small hepatocyte nodus, and minority of them appeared in the nodus. Kupffer cells were mainly limited in the pericentral sinusoids. After day 18, the normal liver Iobule structures began to recover.CONCLUSION: Local hepatic microenvironment may participate in the oval cell-mediated liver regeneration through the cell-cell and cell-matrix interactions.展开更多
AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related ge...AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGE- BSA) and N'-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-α (TNF-α). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS: In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1( I ) mRNA by AGE-BSA. CONCLUSION: Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.展开更多
AIM: To explore a feasible method on the establishment of an animal model of conjunctivochalasis (CCH). METHODS: Twelve clean-grade New Zealand white rabbits were divided into four groups (n=3/group): the contr...AIM: To explore a feasible method on the establishment of an animal model of conjunctivochalasis (CCH). METHODS: Twelve clean-grade New Zealand white rabbits were divided into four groups (n=3/group): the control group (one received no interventions, and the others underwent subconjunctival injection of sterile water), the matrix metalloproteinases (MMPs) group (administered subconjunctival injection of MMP-3), the aging group (administered subcutaneous injection of D-galactose), the tumor necrosis factor-α (TNF-α) solution group (administered eye drops of TNF-α). Anterior segment photography, conjunctival tissue light microscopy and transmission electron microscopy (TEM) were performed after 12wk. RESULTS: Among all groups, the MMPs group had the following changes: the looser connection between the inferior bulbar conjunctiva and sclera; the more disordered collagen fibers (Trichrome staining) and the broken elastic fibers (Aldehyde-fuchsin staining); the focal necrosis of fibroblasts (TEM). CONCLUSION: Administration of MMPs may be a feasible method for the establishment of an animal model of CCH.展开更多
目的:研究上调Smad7表达对肝星形细胞(HSC)α1(Ⅰ)和α1(Ⅲ)前胶原基因转录的作用.方法:应用Fugene6介导Smad7质粒转染体外培养的HSC-T6细胞.继续培养48 h.同时使用实时定量聚合酶链式反应(Real time-PCR),逆转录酶链式反应(RT-PCR)方...目的:研究上调Smad7表达对肝星形细胞(HSC)α1(Ⅰ)和α1(Ⅲ)前胶原基因转录的作用.方法:应用Fugene6介导Smad7质粒转染体外培养的HSC-T6细胞.继续培养48 h.同时使用实时定量聚合酶链式反应(Real time-PCR),逆转录酶链式反应(RT-PCR)方法检测Smad7质粒组和正常对照组、空载质粒对照组α(Ⅰ)和α1(Ⅲ)前胶原mRNA水平.结果:与正常对照组和空载质粒对照组相比,Smad7质粒转染HSC-T6细胞48h后,Smad7 mRNA水平显著增高(1.29±0.18 vs 0.11±0.02,0.13±0.02,均P<0.01),α1(Ⅰ)前胶原mRNA表达明显下降(0.10±0.01 vs 1.18±0.15.1.07±0.12,均P<0.01),但α1(Ⅲ)前胶原基因表达无明显改变(0.72±0.00 vs 0.70±0.01,0.75±0.0l,均P>0.05).结论:Smad7能明显抑制HSC细胞α1(Ⅰ)前胶原mRNA转录.展开更多
The capability of human pluripotent stem cells(h PSCs) to differentiate into a variety of cells in the human body holds great promise for regenerative medicine. Many substrates exist on which h PSCs can be self-renewe...The capability of human pluripotent stem cells(h PSCs) to differentiate into a variety of cells in the human body holds great promise for regenerative medicine. Many substrates exist on which h PSCs can be self-renewed, maintained and expanded to further the goal of clinical application of stem cells. In this review, we highlight numerous extracellular matrix proteins, peptide and polymer based substrates, scaffolds and hydrogels that have been pioneered. We discuss their benefits and shortcomings and offer future directions as well as emphasize commercially available synthetic peptidesas a type of substrate that can bring the benefits of regenerative medicine to clinical settings.展开更多
基金Supported by A grant from National Natural Science Foundation of China
文摘AIM: To elucidate the interaction between non- parenchymal cells, extracellular matrix and oval cells during the restituting process of liver injury induced by partial hepatectomy (PH). METHODS: We examined the localization of oval cells, non-parenchymal cells, and the extracellular matrix components using immunohistochemical and double immunofluorescent analysis during the proliferation and differentiation of oval cells in N-2- acetylaminofluorene (2-AAF)/PH rat model. RESULTS: By day 2 after PH, small oval cells began to proliferate around the portal area. Most of stellate cells and laminin were present along the hepatic sinusoids in the periportal area. Kupffer cells and fibronectin markedly increased in the whole hepatic Iobule. From day 4 to 9, oval cells spread further into hepatic parenchyma, closely associated with stellate cells, fibronectin and laminin. Kupffer cells admixed with oval cells by day 6 and then decreased in the periportal zone. From day 12 to 15, most of hepatic stellate cells (HSCs), laminin and fibronectin located around the small hepatocyte nodus, and minority of them appeared in the nodus. Kupffer cells were mainly limited in the pericentral sinusoids. After day 18, the normal liver Iobule structures began to recover.CONCLUSION: Local hepatic microenvironment may participate in the oval cell-mediated liver regeneration through the cell-cell and cell-matrix interactions.
基金Supported by Grants from the Interdisciplinary Center for Clinical Research(IZKF,Project B39)the Johannes and Frieda Marohn Foundation of the University of Erlangen-Nuremberg,Germany
文摘AIM: To study the role of advanced glycation end products (AGE) and their specific receptor (RAGE) in the pathogenesis of liver fibrogenesis. METHODS: In vitro RAGE expression and extracellular matrix-related gene expression in both rat and human hepatic stellate cells (HSC) were measured after stimulation with the two RAGE ligands, advanced glycation end product-bovine serum albumin (AGE- BSA) and N'-(carboxymethyl) lysine (CML)-BSA, or with tumor necrosis factor-α (TNF-α). In vivo RAGE expression was examined in models of hepatic fibrosis induced by bile duct ligation or thioacetamide. The effects of AGE-BSA and CML-BSA on HSC proliferation, signal transduction and profibrogenic gene expression were studied in vitro. RESULTS: In hepatic fibrosis, RAGE expression was enhanced in activated HSC, and also in endothelial cells, inflammatory cells and activated bile duct epithelia. HSC expressed RAGE which was upregulated after stimulation with AGE-BSA, CML-BSA, and TNF-α.RAGE stimulation with AGE-BSA and CML-BSA did not alter HSC proliferation, apoptosis, fibrogenic signal transduction and fibrosis- or fibrolysis-related gene expression, except for marginal upregulation of procollagen α1( I ) mRNA by AGE-BSA. CONCLUSION: Despite upregulation of RAGE in activated HSC, RAGE stimulation by AGE does not alter their fibrogenic activation. Therefore, RAGE does not contribute directly to hepatic fibrogenesis.
基金Supported by the Key Medical Discipline Project of Shanghai Municipal Health Bureau-Ophthalmology(No.ZK2015A20)the Health System Independent Innovation Science Foundation of Shanghai Putuo District(No.2015PTKW001)Plateau Science,Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine
文摘AIM: To explore a feasible method on the establishment of an animal model of conjunctivochalasis (CCH). METHODS: Twelve clean-grade New Zealand white rabbits were divided into four groups (n=3/group): the control group (one received no interventions, and the others underwent subconjunctival injection of sterile water), the matrix metalloproteinases (MMPs) group (administered subconjunctival injection of MMP-3), the aging group (administered subcutaneous injection of D-galactose), the tumor necrosis factor-α (TNF-α) solution group (administered eye drops of TNF-α). Anterior segment photography, conjunctival tissue light microscopy and transmission electron microscopy (TEM) were performed after 12wk. RESULTS: Among all groups, the MMPs group had the following changes: the looser connection between the inferior bulbar conjunctiva and sclera; the more disordered collagen fibers (Trichrome staining) and the broken elastic fibers (Aldehyde-fuchsin staining); the focal necrosis of fibroblasts (TEM). CONCLUSION: Administration of MMPs may be a feasible method for the establishment of an animal model of CCH.
文摘目的:研究上调Smad7表达对肝星形细胞(HSC)α1(Ⅰ)和α1(Ⅲ)前胶原基因转录的作用.方法:应用Fugene6介导Smad7质粒转染体外培养的HSC-T6细胞.继续培养48 h.同时使用实时定量聚合酶链式反应(Real time-PCR),逆转录酶链式反应(RT-PCR)方法检测Smad7质粒组和正常对照组、空载质粒对照组α(Ⅰ)和α1(Ⅲ)前胶原mRNA水平.结果:与正常对照组和空载质粒对照组相比,Smad7质粒转染HSC-T6细胞48h后,Smad7 mRNA水平显著增高(1.29±0.18 vs 0.11±0.02,0.13±0.02,均P<0.01),α1(Ⅰ)前胶原mRNA表达明显下降(0.10±0.01 vs 1.18±0.15.1.07±0.12,均P<0.01),但α1(Ⅲ)前胶原基因表达无明显改变(0.72±0.00 vs 0.70±0.01,0.75±0.0l,均P>0.05).结论:Smad7能明显抑制HSC细胞α1(Ⅰ)前胶原mRNA转录.
文摘The capability of human pluripotent stem cells(h PSCs) to differentiate into a variety of cells in the human body holds great promise for regenerative medicine. Many substrates exist on which h PSCs can be self-renewed, maintained and expanded to further the goal of clinical application of stem cells. In this review, we highlight numerous extracellular matrix proteins, peptide and polymer based substrates, scaffolds and hydrogels that have been pioneered. We discuss their benefits and shortcomings and offer future directions as well as emphasize commercially available synthetic peptidesas a type of substrate that can bring the benefits of regenerative medicine to clinical settings.