کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6163605 1249438 2014 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ablation of proximal tubular suppressor of cytokine signaling 3 enhances tubular cell cycling and modifies macrophage phenotype during acute kidney injury
ترجمه فارسی عنوان
از بین بردن مهار کننده پروگزیمال لوله ای سیگنالینگ سیتوکین 3 موجب افزایش دوچرخه سواری سلول های لوله ای می شود و فنوتیپ ماکروفاژ را در طول آسیب های شدید کلیه تغییر می دهد
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
چکیده انگلیسی
Suppressor of cytokine signaling 3 (SOCS-3) is an important intracellular negative regulator of several signaling pathways. We found that SOCS-3 is highly expressed in renal proximal tubules during acute kidney injury. To test the impact of this, conditional proximal tubular knockout mice (SOCS-3sglt2Δ/sglt2Δ) were created. These mice had better kidney function than their wild-type counterparts in aristolochic acid nephropathy and after ischemia/reperfusion injury. Kidneys of these knockout mice showed significantly more proximal tubular cell proliferation during the repair phase. A direct effect of SOCS-3 on tubular cell cycling was demonstrated by in vitro experiments showing a JAK/STAT pathway-dependent antimitotic effect of SOCS-3. Furthermore, acute damaged kidneys of the knockout mice contained increased numbers of F4/80+ cells. Phenotypic analysis of these F4/80+ cells indicated a polarization from classically activated to alternatively activated macrophages. In vitro, SOCS-3-overexpressing renal epithelial cells directly induced classical activation in cocultured macrophages, supporting the observed in vivo phenomenon. Thus, upregulation of SOCS-3 in stressed proximal tubules plays an important role during acute kidney injury by inhibition of reparative proliferation and by modulation of the macrophage phenotype. Antagonizing SOCS-3 could have therapeutic potential for acute kidney injury.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 85, Issue 6, June 2014, Pages 1357-1368
نویسندگان
, , , , , , , , , , , ,