کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8949205 | 1666279 | 2018 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Adiponectin inhibits hepatic stellate cell activation by targeting the PTEN/AKT pathway
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
ECMDnmtSOCS-3sirtuinSIRTPPARαCCl4TGFβ1FAKHSCsPTP1Bα-SMAAMPKDNA methyltransferase - DNA متیل ترانسفرازadiponectin - آدیپونکتینα-smooth muscle actin - اکتین عضله آلفا صافTransforming growth factor β1 - تبدیل فاکتور رشد β1suppressor of cytokine signaling-3 - سرکوبگر سیگنالینگ سیتوکین-3Hepatic stellate cell - سلول ستاره ای کبدیLiver fibrosis - فیبروز کبدیExtracellular matrix - ماتریکس خارج سلولیDNA methylation - متیلاسیون DNAMicroRNA - میکرو RNA peroxisome proliferator-activated receptor-α - پراکسیزوم پرولیفراتور فعال گیرنده -αProtein tyrosine phosphatase 1B - پروتئین تیروزین فسفاتاز 1Badenosine monophosphate-activated protein kinase - پروتئین کیناز فعال شده با آدنوزین مونوفسفاتPten - ژن PTENCarbon tetrachloride - کربن تتراکلریدfocal adhesion kinase - کیناز چسبندگی کانونی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Adiponectin inhibits hepatic stellate cell (HSC) activation and subsequent development of liver fibrosis via multiple mechanisms. Phosphatase and tensin homolog deletion 10 (PTEN) plays a crucial role in suppression of HSC activation, but its regulation by adiponectin is not fully understood. Here, we investigated the effect of adiponectin on PTEN in LX-2 cells, a human cell line and examined the underlying molecular mechanisms involved in adiponectin-mediated upregulation of PTEN activity during fibrosis. PTEN expression was found to be significantly reduced in the livers of mice treated with CCl4, whereas its expression was rescued by adiponectin treatment. The DNA methylation proteins DNMT1, DNMT3A, and DNMT3B are all highly expressed in activated primary HSCs compared to quiescent HSCs, and thus represent additional regulatory targets during liver fibrogenesis. Expression of DNMT proteins was significantly induced in the presence of fibrotic stimuli; however, only DNMT3B expression was reduced in the presence of adiponectin. Adiponectin-induced suppression of DNMT3B was found to be mediated by enhanced miR-29b expression. Furthermore, PTEN expression was significantly increased by overexpression of miR-29b, whereas its expression was markedly reduced by a miR-29b inhibitor in LX-2 cells. These findings suggest that adiponectin-induced upregulation of miR-29b can suppress DNMT3B transcription in LX-2 cells, thus resulting in reduced methylation of PTEN CpG islands and ultimately suppressing the PI3K/AKT pathway. Together, these data suggest a possible new explanation for the inhibitory effect of adiponectin on HSC activation and liver fibrogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 10, October 2018, Pages 3537-3545
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 10, October 2018, Pages 3537-3545
نویسندگان
Pradeep Kumar, Reben Raeman, Daniel M. Chopyk, Tekla Smith, Kiran Verma, Yunshan Liu, Frank A. Anania,