title: Different regulation of miR-29a-3p in glomeruli and tubules in an experimental model of angiotensin II-dependent hypertension: potential role in renal fibrosis.
abstract: The aim of this study was to evaluate the role of the angiotensin II (Ang II) induced-differential miRNA expression in renal glomerular and tubulo-interstitial fibrosis in an experimental model of Ang II-dependent hypertension. To clarify this issue, Sprague Dawley rats were treated with Ang II (200 ng/kg per minute, n = 15) or physiological saline (n = 14) for 4 weeks. Systolic blood pressure and albuminuria were measured every 2 weeks. At the end of the experimental period, renal glomerular and tubulo-interstitial fibrosis was evaluated by histomorphometric analysis, after Sirius-Red and Masson's trichrome staining. Ang II increased systolic blood pressure (P < 0.0001), albuminuria (P < 0.01) and both glomerular and tubulo-interstitial fibrosis (P < 0.01). Using laser capture microdissection and miRNA microarray analysis this study showed that miR-29a-3p was down-regulated in renal tubules and up-regulated in glomeruli. Real-time polymerase chain reaction (PCR) experiments confirmed in Ang II-treated rats a down-regulation of miR-29a-3p in tubules (P < 0.01), while no significant changes were observed in glomeruli. Matrix metalloproteinase-2 (MMP-2) was identified as putative miR-29a-3p target (by TargetScan, miRanda, Tarbase software) and functionally confirmed by luciferase activity assay. These data demonstrate that the effects of Ang II on miR-29a-3p expression in renal tubules is different from the one exerted in the glomeruli and that miR-29a-3p targets MMP-2. These results suggest that the development of renal fibrosis at glomerular and tubulo-interstitial level depends on different molecular mechanisms.
authors.affiliation: Clinica Nefrologica, Az. Osp. San Gerardo, Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Monza.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Castoldi
authors.affiliation: Dipartimento di Scienze Radiologiche, Oncologiche ed Anatomo-Patologiche, Sapienza Università di Roma, Rome.
authors.forename: Cira
authors.initials: C
authors.lastname: di Gioia
authors.affiliation: Dipartimento di Informatica, Sistemistica e Comunicazione. Università degli Studi di Milano-Bicocca, Milan.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Giollo
authors.affiliation: Dipartimento di Scienze Radiologiche, Oncologiche ed Anatomo-Patologiche, Sapienza Università di Roma, Rome.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Carletti
authors.affiliation: Clinica Nefrologica, Az. Osp. San Gerardo, Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Monza.
authors.forename: Camila
authors.initials: C
authors.lastname: Bombardi
authors.affiliation: Dipartimento di Informatica, Sistemistica e Comunicazione. Università degli Studi di Milano-Bicocca, Milan.
authors.forename: Marco
authors.initials: M
authors.lastname: Antoniotti
authors.affiliation: Clinica Nefrologica, Az. Osp. San Gerardo, Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Monza.
authors.forename: Francesca
authors.initials: F
authors.lastname: Roma
authors.affiliation: Unita' Complicanze del Diabete, Istituto Scientifico San Raffaele, Milan, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Zerbini
authors.affiliation: Clinica Nefrologica, Az. Osp. San Gerardo, Dipartimento di Medicina e Chirurgia, Università degli Studi di Milano-Bicocca, Monza.
authors.forename: Andrea
authors.initials: A
authors.lastname: Stella
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000235:genetics; D006973:Hypertension / Q000235:genetics* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2
keywords: Angiotensin II; miR-29a-3p; microRNA; rats; renal fibrosis