title: miR-21 and miR-214 are consistently modulated during renal injury in rodent models.
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.
authors.affiliation: BHF Glasgow Cardiovascular Research Centre, Glasgow, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Denby
authors.forename: Vasudev
authors.initials: V
authors.lastname: Ramdas
authors.forename: Martin W
authors.initials: MW
authors.lastname: McBride
authors.forename: Joe
authors.initials: J
authors.lastname: Wang
authors.forename: Hollie
authors.initials: H
authors.lastname: Robinson
authors.forename: John
authors.initials: J
authors.lastname: McClure
authors.forename: Wendy
authors.initials: W
authors.lastname: Crawford
authors.forename: Ruifang
authors.initials: R
authors.lastname: Lu
authors.forename: Dianne Z
authors.initials: DZ
authors.lastname: Hillyard
authors.forename: Raya
authors.initials: R
authors.lastname: Khanin
authors.forename: Reuven
authors.initials: R
authors.lastname: Agami
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.forename: Claire C
authors.initials: CC
authors.lastname: Sharpe
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000378:metabolism; D006973:Hypertension / Q000473:pathology; D007668:Kidney / Q000293:injuries / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014513:Ureter / Q000473:pathology
chemical_list: D035683:MicroRNAs; C559947:Mirn214 microRNA, rat; D016212:Transforming Growth Factor beta; C546082:mirn21 microRNA, rat