کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1905002 1534683 2012 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Overexpression of insulin like growth factor binding protein 5 reduces liver fibrosis in chronic cholangiopathy
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Overexpression of insulin like growth factor binding protein 5 reduces liver fibrosis in chronic cholangiopathy
چکیده انگلیسی

The ATP-binding cassette, sub-family B member 4 knock-out mouse (Abcb4−/−) is a relevant model for chronic cholangiopathy in man. Due to the lack of this P-glycoprotein in the canalicular membrane of hepatocytes, the secretion of phospholipids into bile is absent, resulting in increased bile toxicity. Expression of insulin like growth factor binding protein 5 (Igfbp5) increases in time in the livers of these mice. It is unclear whether this induction is a consequence of or plays a role in the progression of liver pathology. The aim of this study was therefore to investigate the effect of IGFBP5 induction on the progression of liver fibrosis caused by chronic cholangiopathy. IGFBP5 and, as a control, green fluorescent protein were overexpressed in the hepatocytes of Abcb4−/− mice, using an adeno-associated viral vector (AAV). Progression of liver fibrosis was studied 3, 6, and 12 weeks after vector injection by analyzing serum parameters, collagen deposition, expression of pro-fibrotic genes, inflammation and oxidative stress. A single administration of the AAV vectors provided prolonged expression of IGFBP5 and GFP in the livers of Abcb4−/− mice. Compared to GFP control, fractional liver weight, extracellular matrix deposition and amount of activated hepatic stellate cells significantly decreased in IGFBP5 overexpressing mice even 12 weeks after treatment. This effect was not due to a change in bile composition, but driven by reduced inflammation, oxidative stress, and proliferation. Overexpression of IGFBP5 seems to have a protective effect on liver pathology in this model for chronic cholangiopathy.


► IGFBP5 was overexpressed in the livers of Abcb4−/− mice using AAV-delivery.
► ECM deposition significantly decreased with IGFBP5 overexpression.
► Hepatocyte proliferation, inflammation and oxidative stress were reduced by IGFBP5.
► Overexpression of IGFBP5 reduces liver fibrosis caused by chronic cholangiopathy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1822, Issue 6, June 2012, Pages 996–1003
نویسندگان
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