miR-21 and miR-214 are consistently modulated during renal injury in rodent models

Denby, L. et al. (2011) miR-21 and miR-214 are consistently modulated during renal injury in rodent models. American Journal of Pathology, 179(2), pp. 661-672. (doi: 10.1016/j.ajpath.2011.04.021)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Baker, Professor Andrew and McBride, Dr Martin and Beattie, Mrs Wendy and Denby, Dr Laura and Lu, Dr Ruifang and Dominiczak, Professor Anna and Hillyard, Ms Dianne and McClure, Dr John
• Authors: Denby, L., Ramdas, V., McBride, M.W., Wang, J., Robinson, H., McClure, J., Crawford, W., Lu, R., Hillyard, D.Z., Khanin, R., Agami, R., Dominiczak, A.F., Sharpe, C. C., and Baker, A.H.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: American Journal of Pathology
• ISSN: 0002-9440
• ISSN (Online): 1525-2191
• Published Online: 31 May 2011