کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3883608 1249432 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
mTOR and rapamycin in the kidney: signaling and therapeutic implications beyond immunosuppression
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
mTOR and rapamycin in the kidney: signaling and therapeutic implications beyond immunosuppression
چکیده انگلیسی

The immunosuppressive drug rapamycin has helped to identify a large signaling network around the target of rapamycin (TOR) protein that integrates information on nutrient availability and growth factors to control protein synthesis and cell size. Studies using rapamycin in animal models of kidney disease indicate that mTOR deregulation has a role in glomerular disease, polycystic kidney disease, and renal cancer. The role of mTOR activation in podocytes is context dependent, and indirect evidence suggests that mTOR may have a role in chronic podocyte loss. Several lines of evidence show that cyst formation in polycystic kidney disease (PKD) involves mTOR activation and its upstream regulator TSC. Polycystin 1 regulates mTOR activity through different pathways, and TSC intersects with the primary cilium, a crucial cell organelle in the pathogenesis of PKD. Data from hamartoma syndromes provide clear evidence that mutation of members of the mTOR network results in renal cancers. The detailed analysis of renal cell carcinomas has revealed a positive feedback loop involving VHL and mTOR. Rapamycin and its derivatives have been approved for the treatment of advanced renal cancer and are being investigated for the treatment of PKD. Discrepancies exist between the effects of rapamycin in animal models and the clinical experience with patients, precluding the widespread use of mTOR inhibitors in kidney disease. The details of mTOR signaling in the kidney need to be clarified to hopefully develop targeted treatments for renal disease in the future.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 79, Issue 5, 1 March 2011, Pages 502–511
نویسندگان
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