کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8533049 1560452 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathy
ترجمه فارسی عنوان
یک آنتاگونیست گیرنده پروتئینی فعال در مقابل آسیب های متابولیک در یک مدل موسوم به نفروپاتی محافظت می کند
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
چکیده انگلیسی
The kidney expresses protease-activated receptor-1 (PAR-1). PAR-1 is known as a thrombin receptor, but its role in kidney injury is not well understood. In this study, we examined the contribution of PAR-1 to kidney glomerular injury and the effects of its inhibition on development of nephropathy. Mice were divided into 3 groups: control, doxorubicin + vehicle (15 mg/kg doxorubicin and saline) and doxorubicin + Q94 (doxorubicin at 15 mg/kg and the PAR-1 antagonist Q94 at 5 mg/kg/d) groups. Where indicated, doxorubicin was administered intravenously and PAR-1 antagonist or saline vehicle by subcutaneous osmotic mini-pump. PAR-1 expression was increased in glomeruli of mice treated with doxorubicin. Q94 treatment significantly suppressed the increased albuminuria in these nephropathic mice. Pathological analysis showed that Q94 treatment significantly attenuated periodic acid-Schiff and desmin staining, indicators of podocyte injury, and also decreased glomerular levels of podocin and nephrin. Furthermore, thrombin increased intracellular calcium levels in podocytes. This increase was suppressed by Q94 and Rox4560, a transient receptor potential cation channel (TRPC)3/6 antagonist. In addition, both Q94 and Rox4560 suppressed the doxorubicin-induced increase in activities of caspase-9 and caspase-3 in podocytes. These data suggested that PAR-1 contributes to development of podocyte and glomerular injury and that PAR-1 antagonists have therapeutic potential.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmacological Sciences - Volume 135, Issue 2, October 2017, Pages 81-88
نویسندگان
, , , , , , , , , , , , , ,