کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3314919 1211227 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های گوارشی
پیش نمایش صفحه اول مقاله
Liver fibrosis induced by hepatic overexpression of PDGF-B in transgenic mice
چکیده انگلیسی

Background/AimsIn hepatic fibrogenesis, stellate cells are activated leading to production and deposition of extracellular matrix. To clarify the role of PDGF-B in liver fibrogenesis, we overexpressed PDGF-B in the liver of transgenic mice.MethodsTransgenic mice for the conditional overexpression of PDGF-B in the liver under control of an albumin promoter were generated utilising the Cre/loxP system. Constitutive PDGF-B expression was achieved after breeding with mice expressing Cre-recombinase under actin promoter control. Tamoxifen inducible expression was achieved after breeding with mice expressing Cre under transthyretin receptor promoter control. Levels of fibrosis were assessed and the expression of regulators of matrix remodelling was measured.ResultsPDGF-B expression caused hepatic stellate cell and myofibroblast activation marked by alpha-smooth muscle actin and PDGFR-β expression. Liver fibrosis was verified macroscopically, histologically and by collagen I mRNA quantification in 4–6 week-old animals. MMP-2, MMP-9 and TIMP-1 were upregulated whereas TGF-β expression was unchanged.ConclusionsWe identified PDGF-B as a proliferative and profibrogenic stimulus and potential inducer of stellate cell transdifferentiation in vivo. PDGF-B overexpression causes liver fibrosis without significantly upregulating TGF-β1, suggesting a TGF-β-independent mechanism. The established model provides a tool for testing anti-PDGF-B therapeutic strategies in liver fibrosis in vivo.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Hepatology - Volume 45, Issue 3, September 2006, Pages 419–428
نویسندگان
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