دورية أكاديمية

miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation.

التفاصيل البيبلوغرافية
العنوان: miR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by HIF-α activation.
المؤلفون: Yi Fang, Xiaofang Yu, Yong Liu, Kriegel, Alison J., Yanyan Heng, Xialian Xu, Mingyu Liang, Xiaoqiang Ding
المصدر: American Journal of Physiology: Renal Physiology; May2013, Vol. 304 Issue 10, pF1274-F1282, 9p
مصطلحات موضوعية: RENAL fibrosis, HYPOXIA-inducible factors, MICRORNA, MIMOSINE, GENE expression, IGA glomerulonephritis, TROPOMYOSINS, LABORATORY rats
مستخلص: Treatment with L-mimosine, which activates hypoxia-inducible factor-α (HIF-α), attenuates renal tubulointerstitial injury and improves renal function in a rat remnant kidney model. The miR-29 family of microRNAs directly targets a large number of extracellular matrix genes and reduces renal interstitial fibrosis. We analyzed microRNA expression profiles in rat remnant kidneys with or without treatment with L-mimosine. The expression of miR-29c was downregulated in rat remnant kidneys compared with sham control and significantly restored by the Lmimosine treatment. In cultured human kidney epithelial HK2 cells, cobalt chloride activated HIF-α and upregulated miR-29c expression. The upregulation of miR-29c expression was significantly attenuated by knockdown of HIF-1α or HIF-2α. Downregulation of miR-29c was associated with significant increases in interstitial fibrosis, collagen type II α1 (COL2A1) protein, and tropomyosin 1α (TPM1) protein in rat remnant kidneys and in kidneys from IgA nephropathy patients. The increases in rat remnant kidneys were attenuated by the L-mimosine treatment. COL2A1 and TPM1 were confirmed to be new, direct targets of miR-29c. In conclusion, miR-29c, an antifibrotic microRNA, is upregulated by HIF-α activation. MiR-29c is downregulated in renal interstitial fibrosis in humans and rats and restored by activation of HIF-α that attenuates fibrosis. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:1931857X
DOI:10.1152/ajprenal.00287.2012