Research ArticlePhysiology

TGF-β Induces Acetylation of Chromatin and of Ets-1 to Alleviate Repression of miR-192 in Diabetic Nephropathy

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Science Signaling  04 Jun 2013:
Vol. 6, Issue 278, pp. ra43
DOI: 10.1126/scisignal.2003389

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Kidney Fibrosis Through Acetylation

Epigenetic changes alter gene expression and can induce pathogenesis. MicroRNA-192 (miR-192) mediates the transcription of genes involved in kidney fibrosis in response to high glucose–induced signaling by TGF-β (transforming growth factor–β). Kato et al. found that in basal conditions, Ets-1 was bound to chromatin upstream of miR-192 and suppressed its expression in murine kidney mesangial cells. After treatment with high glucose or TGF-β, Ets-1 was acetylated in an Akt- and p300-dependent manner and dissociated from miR-192. Although Ets-1 was dispensable for transiently increased expression of miR-192, Ets-1 deficiency in mice or murine mesangial cells prevented the sustained expression of miR-192 in response to TGF-β. Activation of p300 and acetylation of Ets-1 and of histone H3 at lysines 9 and 14 were increased in diabetic db/db mice compared with wild-type mice, suggesting that alleviation of Ets-1 repression may contribute to diabetic nephropathy.

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