Dataset Information

MicroRNA-21 in glomerular injury.

ABSTRACT: TGF-?(1) 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-?(1), and miR-21 inhibits apoptosis in cancer cells. TGF-?(1)-transgenic mice exhibit accelerated podocyte loss and glomerulosclerosis. We determined that miR-21 expression increases rapidly in cultured murine podocytes after exposure to TGF-?(1) and is higher in kidneys of TGF-?(1)-transgenic mice than wild-type mice. miR-21-deficient TGF-?(1)-transgenic mice showed increased proteinuria and glomerular extracellular matrix deposition and fewer podocytes per glomerular tuft compared with miR-21 wild-type TGF-?(1)-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 in the rate of cell death, TGF-?/Smad3-signaling activity, and expression of known proapoptotic miR-21 target genes p53, Pdcd4, Smad7, Tgfbr2, and Timp3. In American-Indian patients with diabetic nephropathy (n=48), albumin-to-creatinine ratio was positively associated with miR-21 expression in glomerular fractions (r=0.6; P<0.001) but not tubulointerstitial fractions (P=0.80). These findings suggest that miR-21 ameliorates TGF-?(1) and hyperglycemia-induced glomerular injury through repression of proapoptotic signals, thereby inhibiting podocyte loss. This finding is in contrast to observations in murine models of tubulointerstitial kidney injury but consistent with findings in cancer models. The aggravation of glomerular disease in miR-21-deficient mice and the positive association with albumin-to-creatinine ratio in patients with diabetic nephropathy support miR-21 as a feedback inhibitor of TGF-? signaling and functions.

SUBMITTER: Lai JY

PROVIDER: S-EPMC4378097 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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MicroRNA-21 in glomerular injury.

Lai Jennifer Y JY Luo Jinghui J O'Connor Christopher C Jing Xiaohong X Nair Viji V Ju Wenjun W Randolph Ann A Ben-Dov Iddo Z IZ Matar Regina N RN Briskin Daniel D Zavadil Jiri J Nelson Robert G RG Tuschl Thomas T Brosius Frank C FC Kretzler Matthias M Bitzer Markus M

Journal of the American Society of Nephrology : JASN 20140821 4

TGF-β(1) 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-β(1), and miR-21 inhibits apoptosis in cancer cells. TGF-β(1)-transgenic mice exhibit accelerated podocyte loss and glomerulosclerosis. We determined that miR-21 expression increases rapidly in cultured murine podocytes after exposure to TGF-β(1) and is higher in kidneys of TGF-β(1)-transgenic mice than wild-t ...[more]

PMID: 25145934

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Dataset Information

MicroRNA-21 in glomerular injury.

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MicroRNA-21 in glomerular injury.

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