Different regulation of miR-29a-3p in glomeruli and tubules in an experimental model of angiotensin II-dependent hypertension: Potential role in renal fibrosis

Giovanna Castoldi, Cira di Gioia, Fabrizio Giollo, Raffaella Carletti, Camila Bombardi, Marco Antoniotti, Francesca Roma, Gianpaolo Zerbini, Andrea Stella

Research output: Contribution to journalArticlepeer-review

Abstract

Summary: 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.

Original languageEnglish
Pages (from-to)335-342
Number of pages8
JournalClinical and Experimental Pharmacology and Physiology
Volume43
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Keywords

  • Angiotensin II
  • MicroRNA
  • MiR-29a-3p
  • Rats
  • Renal fibrosis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Pharmacology

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