The role of the mammalian target of rapamycin (mTOR) in renal disease.
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a pivotal role in mediating cell size and mass, proliferation, and survival. mTOR has also emerged as an important modulator of several forms of renal disease. mTOR is activated after acute kidney injury and contributes to renal regeneration and repair. Inhibition of mTOR with rapamycin delays recovery of renal function after acute kidney injury. Activation of mTOR within the kidney also occurs in animal models of diabetic nephropathy and other causes of progressive kidney disease. Rapamycin ameliorates several key mechanisms believed to mediate changes associated with the progressive loss of GFR in chronic kidney disease. These include glomerular hypertrophy, intrarenal inflammation, and interstitial fibrosis. mTOR also plays an important role in mediating cyst formation and enlargement in autosomal dominant polycystic kidney disease. Inhibition of mTOR by rapamycin or one of its analogues represents a potentially novel treatment for autosomal dominant polycystic kidney disease. Finally, inhibitors of mTOR improve survival in patients with metastatic renal cell carcinoma.
Lieberthal
Wilfred
W
Stony Brook Medical Center, Health Sciences Center, 16-081B Nicholls Road, Stony Brook, NY 11794-8166, USA. wlieberthal@notes.cc.sunysb.edu
Levine
Jerrold S
JS
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000209:etiology / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000293:injuries / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D052177:Kidney Diseases, Cystic / Q000209:etiology / Q000503:physiopathology; D007680:Kidney Neoplasms / Q000209:etiology / Q000503:physiopathology; D000076222:Mechanistic Target of Rapamycin Complex 1; D008954:Models, Biological; D046912:Multiprotein Complexes; D016891:Polycystic Kidney, Autosomal Dominant / Q000209:etiology / Q000503:physiopathology; D011494:Protein Kinases / Q000502:physiology*; D011506:Proteins; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000502:physiology
D046912:Multiprotein Complexes; D011506:Proteins; D014157:Transcription Factors; D011494:Protein Kinases; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases