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)

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Publisher's URL: http://dx.doi.org/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 Denby, Dr Laura and Lu, Dr Ruifang and McBride, Dr Martin and Dominiczak, Professor Anna and Beattie, Mrs Wendy 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 > Institute of Cardiovascular and Medical Sciences
Journal Name:American Journal of Pathology
ISSN:0002-9440
ISSN (Online):1525-2191
Published Online:31 May 2011

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