کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3887743 1249597 2009 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Late progression of renal pathology and cyst enlargement is reduced by rapamycin in a mouse model of nephronophthisis
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Late progression of renal pathology and cyst enlargement is reduced by rapamycin in a mouse model of nephronophthisis
چکیده انگلیسی

Because the size of renal cysts in the native kidneys of patients with ADPKD who have been transplanted was found to be reduced when rapamycin was the immunosuppressant, we tested the involvement of the mTOR pathway in cyst enlargement. Here, male pcy mice, with mutation in one of the nephronophthisis genes, were treated with rapamycin at an early (6 to12 weeks of age) or a later (20 to 30 weeks of age) disease stage by means of slow-release pellets containing placebo or rapamycin. Effectiveness of the rapamycin dose and delivery was shown by the inhibition of insulin-stimulated phosphorylation of p70S6K, a marker of mTOR activity, in skeletal muscle. Early treatment did not affect initial cyst development but when started late, there was a significant reduction in the rate of cyst enlargement, kidney fibrosis, and the progressive loss of renal function as measured by blood urea nitrogen. Kidneys of the mice treated through 30 weeks of age tended to be smaller and have less fibrosis compared with those of untreated or placebo-treated pcy/pcy mice at 20 weeks when treatment was initiated. Our study shows that rapamycin can prevent the late- but not the early-stage progression of renal pathology and deterioration of renal functional in this model of nephronophthisis, presumably by inhibiting mTOR activity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 76, Issue 2, 2 July 2009, Pages 178–182
نویسندگان
, , , ,