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Role of the receptor for advanced glycation end products in hepatic fibrosis

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World Journal of Gastroenterology 2009年第46期15卷 5789-5798页

作者： Christina Lohwasser Daniel Neureiter Yury Popov Michael Bauer Detlef Schuppan Department of Medicine Ⅰ University of Erlangen-NurembergErlangen-Nürnberg Institute of Pathology Paracelsus Private Medicine UniversitySalzburg Division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBoston

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.

关键词： Advanced glycation end product extracellularmatrix Hepatic stellate cell Matrix metalloproteinase Myofibroblast Receptor for advanced glycation endproducts Transforming growth factor β Tissue inhibitorof metalloproteinase Tumor necrosis factor α

Qiguiyishen decoction reduced the accumulation of extracellular matrix in the kidneys of rats with adriamycin-induced nephropathy

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Journal of Traditional Chinese Medicine 2014年第3期34卷 351-356页

作者： Minggang Wei Wei Sun Weiming He Li Ni Xiaofeng Cai Zongqi Cheng Kun Gao Fengling Li Lin Chen Xinping Zhang the Department of Integrated Traditional and Western Medicine the First Affiliated Hospital of Soochow University the DepartmentofKidney Disease Jiangsu Province Hospital of Traditional Chinese Medicine

OBJECTIVE： To investigate the effect of Qiguiyish- en decoction （QGYS） on the severity of nephropa- thy. METHODS： Twenty-four rats were randomly divid- ed into four groups （ Ⅰ,Ⅱ,Ⅲ, IV） according to the random number table. Group I as control group did not establish nephropathy model. Groups Ⅱ, Ⅲ, and IV were intravenously administered Adria- mycin （7.5 mg/kg） through the tail vein to establish nephropathy model. QGYS was prepared with the extracts of Huangqi （RadixAstragali Mongolici）, Dan- ggui （Radix Angelicae Sinensis）, Niuxi （Radix Achyran-this Bidentatae）, and Chuanxiong （Rhizoma Chuanx- iong）. Group IV was administered QGYS （2 mL. kg^-1· d^-1）, groupⅢ was administered benazepril （10 mL. kg^-1·d^-1）, and group ⅠⅡ was administered water （2 mL. kg·^-1. d^-1） once daily for eight weeks. RESULTS： QGYS reduced the excretion of urinary protein and N-acetyH3-D-glucosaminidase and alle- viated the accumulation of extracellular matrix （ECM） in renal tissue. Additionally, QGYS effectively regulated the levels of transforming growth factor, tissue inhibitor of matrix metalloproteinase, and matrix metalloproteinases in the kidney of the rats. CONCLUSION-＂ QGYS may reduce the accumulation of ECM in the kidneys of rats with Adriamycin-in- duced nephropathy.

关键词： Qiguiyishen decoction extracellularmatrix Doxorubicin Nephrosis

A preliminary study on the establishment of an animal model of conjunctivochalasis

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International Journal of Ophthalmology(English edition) 2018年第6期11卷 899-904页

作者： Jing-Yun Gan Qing-Song Li Huan-Ming Zhou Wei Zhang Ling-Zhi Lian Zhang Yu Zhen-Yong Zhang Department of Ophthalmology Putuo Hospital Shanghai University of Traditional Chinese Medicine Department of Pathology Putuo Hospital Shanghai University of Traditional Chinese Medicine Department of Electron Microscopy Shanghai Medical College Fudan University

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.

关键词： animal model conjunctivochalasis extracellularmatrix inflammatory factors matrix metalloproteinase

Substrates for clinical applicability of stem cells

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World Journal of Stem Cells 2015年第2期7卷 243-252页

作者： Sanjar Enam Sha Jin Department of Biomedical Engineering Thomas J Watson School of Engineering and Applied SciencesState University of New York in Binghamton

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.

关键词： Human pluripotent stem cells extracellularmatrix protein Synthetic substrate Peptide Polymer Scaffold Hydrogel