TY - JOUR
T1 - miR-21 and miR-214 Are Consistently Modulated during Renal Injury in Rodent Models
AU - Denby, Laura
AU - Ramdas, Vasudev
AU - McBride, Martin W.
AU - Wang, Joe
AU - Robinson, Hollie
AU - McClure, John
AU - Crawford, Wendy
AU - Lu, Ruifang
AU - Hillyard, Dianne Z.
AU - Khanin, Raya
AU - Agami, Reuven
AU - Dominiczak, Anna F.
AU - Sharpe, Claire C.
AU - Baker, Andrew H.
PY - 2011/8
Y1 - 2011/8
N2 - Transforming growth factor (TGF)-beta 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-beta-induced expression of miR-21, miRNAs in cell culture models and miRNA expression in relevant models of renal disease. In vitro, TGF-beta 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-beta. TGF-beta 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-beta 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. (Am J Pathol 2011, 170:661-672; DOI: 10.1016/j.ajpath.2011.04.021)
AB - Transforming growth factor (TGF)-beta 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-beta-induced expression of miR-21, miRNAs in cell culture models and miRNA expression in relevant models of renal disease. In vitro, TGF-beta 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-beta. TGF-beta 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-beta 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. (Am J Pathol 2011, 170:661-672; DOI: 10.1016/j.ajpath.2011.04.021)
U2 - 10.1016/j.ajpath.2011.04.021
DO - 10.1016/j.ajpath.2011.04.021
M3 - Article
VL - 179
SP - 661
EP - 672
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 2
ER -