MicroRNA-21 in Glomerular Injury (original) (raw)

Journal of the American Society of Nephrology : JASN, 2015

Abstract

TGF-β1 is a pleotropic growth factor that mediates glomerulosclerosis and podocyte apoptosis, hallmarks of glomerular diseases. The expression of microRNA-21 (miR-21) is regulated by TGF-β1, and miR-21 inhibits apoptosis in cancer cells. TGF-β1-transgenic mice exhibit accelerated podocyte loss and glomerulosclerosis. We determined that miR-21 expression increases rapidly in cultured murine podocytes after exposure to TGF-β1 and is higher in kidneys of TGF-β1-transgenic mice than wild-type mice. miR-21-deficient TGF-β1-transgenic mice showed increased proteinuria and glomerular extracellular matrix deposition and fewer podocytes per glomerular tuft compared with miR-21 wild-type TGF-β1-transgenic littermates. Similarly, miR-21 expression was increased in streptozotocin-induced diabetic mice, and loss of miR-21 in these mice was associated with increased albuminuria, podocyte depletion, and mesangial expansion. In cultured podocytes, inhibition of miR-21 was accompanied by increases i...

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