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

Laura Denby, Vasudev Ramdas, Martin W McBride, Joe Wang, Hollie Robinson, John McClure, Wendy Crawford, Ruifang Lu, Dianne Z Hillyard, Raya Khanin, Reuven Agami, Anna F Dominiczak, Claire C Sharpe, Andrew H Baker

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)661-72
Number of pages12
JournalAmerican Journal of Pathology
Volume179
Issue number2
DOIs
Publication statusPublished - Aug 2011

Keywords

  • Animals
  • Disease Models, Animal
  • Gene Expression Regulation
  • Glomerulonephritis
  • Hypertension
  • Kidney
  • Kidney Glomerulus
  • Kidney Tubules
  • Male
  • MicroRNAs
  • Rats
  • Rats, Inbred WKY
  • Time Factors
  • Transforming Growth Factor beta
  • Ureter

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