Li Szu Yuan, Susztak Katalin
J Clin Invest. 2016 Nov 1;126(11):4072-4075. doi: 10.1172/JCI90828. Epub 2016 Oct 17.
An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice. Together, these results highlight an important connection between lncRNA-mediated metabolic alterations in podocytes and kidney disease development.
越来越多的证据表明,代谢改变在慢性肾脏病(CKD)发病机制中起关键作用。在本期《临床研究杂志》中,Long等人报道长链非编码RNA(lncRNA)牛磺酸上调基因1(Tug1)促进CKD的发展。作者表明,Tug1通过对转录因子PPARγ共激活因子1α(由Ppargc1a编码的PGC-1α)的表达进行表观遗传靶向调控,来调节足细胞中的线粒体功能。在小鼠足细胞中特异性过表达Tug1可改善糖尿病诱导的CKD。这些结果共同凸显了lncRNA介导的足细胞代谢改变与肾脏疾病发展之间的重要联系。