Research ArticleFibrosis

Long noncoding RNA lnc-TSI inhibits renal fibrogenesis by negatively regulating the TGF-β/Smad3 pathway

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Science Translational Medicine  10 Oct 2018:
Vol. 10, Issue 462, eaat2039
DOI: 10.1126/scitranslmed.aat2039

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A target for renal fibrosis

Transforming growth factor–β (TGF-β) is a known regulator of fibrosis but has remained difficult to target. Wang et al. identified a kidney-specific long noncoding RNA, lnc-TSI, that inhibited Smad3 activation and downstream profibrogenic gene expression in human tubular epithelial cells (TECs). Ectopic lnc-TSI expression in mouse TECs confirmed inhibition of TGF-β signaling, and delivery of lnc-TSI in unilateral ureteral obstruction and ischemic reperfusion injury–induced fibrosis models resulted in reduced renal fibrogenesis. Expression of lnc-TSI negatively correlated with fibrosis and renal failure in IgA nephropathy patients, raising the possibility that the lncRNA could be a potential therapeutic target.