Regular article
Cardiovascular, pulmonary, and renal pathology
miR-21 and miR-214 Are Consistently Modulated during Renal Injury in Rodent Models

https://doi.org/10.1016/j.ajpath.2011.04.021Get rights and content
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Transforming growth factor (TGF)-β is one of the main fibrogenic cytokines that drives the pathophysiology of progressive renal scarring. MicroRNAs (miRNAs) are endogenous non-coding RNAs that post-transcriptionally regulate gene expression. We examined the role of TGF-β–induced expression of miR-21, miRNAs in cell culture models and miRNA expression in relevant models of renal disease. In vitro, TGF-β changed expression of miR-21, miR-214, and miR-145 in rat mesangial cells (CRL-2753) and miR-214, miR-21, miR-30c, miR-200b, and miR-200c during induction of epithelial-mesenchymal transition in rat tubular epithelial cells (NRK52E). miR-214 expression was robustly modulated in both cell types, whereas in tubular epithelial cells miR-21 was increased and miR-200b and miR-200c were decreased by 58% and 48%, respectively, in response to TGF-β. TGF-β receptor-1 was found to be a target of miR-200b/c and was down-regulated after overexpression of miR-200c. To assess the differential expression of these miRNAs in vivo, we used the anti-Thy1.1 mesangial glomerulonephritis model and the unilateral ureteral obstruction model in which TGF-β plays a role and also a genetic model of hypertension, the stroke-prone spontaneously hypertensive rat with and without salt loading. The expressions of miR-214 and miR-21 were significantly increased in all in vivo models, showing a possible miRNA signature of renal damage despite differing causes.

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Supported by Kidney Research UK, British Heart Foundation Chair, and Programe Grants (RG/09/005/27915 and BHFRG/07/005/23633) and by a pump priming grant from the Integrative Mammalian Biology Initiative at the University of Glasgow.

Supplemental material for this article can be found at http://ajp.amjapthol.org or at doi: 10.1016/j.ajpath.2011.04.021.