Metformin prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction

Rita C. Cavaglieri, Robert T. Day, Denis Feliers, Hanna E. Abboud

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Unilateral ureteral obstruction causes important tubulo-interstitial fibrosis in the kidney. Metformin reduces fibrosis in mice with diabetic nephropathy. We examined the effects of metformin in a mouse model of unilateral ureteral obstruction (UUO). Expression of inflammation and fibrosis markers was studied by immunohistochemistry, immunoblot and quantitative real-time polymerase chain reaction. Seven days after UUO, kidneys presented dilated tubules, expansion of the tubulo-interstitial compartment, and significant infiltration of inflammatory cells. Macrophage infiltration and inflammation markers expression were increased in obstructed kidneys and reduced by metformin. Metformin reduced expression of extracellular matrix proteins and profibrotic factor TGFβ in obstructed kidneys, measured by immunohistochemistry. Interstitial fibroblast activation was evident in obstructed kidneys and ameliorated by metformin. UUO did not affect adenosine monophosphate-activated kinase (AMPK) activity, but metformin activated AMPK. Our results show that metformin prevents or slows down the onset of renal inflammation and fibrosis in mice with UUO, an effect that could be mediated by activation of AMPK.

Original languageEnglish (US)
Pages (from-to)116-122
Number of pages7
JournalMolecular and Cellular Endocrinology
Volume412
DOIs
StatePublished - Sep 5 2015

Keywords

  • Adenosine monophosphate-activated kinase
  • Fibrosis
  • Inflammation
  • Kidney
  • Metformin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Fingerprint

Dive into the research topics of 'Metformin prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction'. Together they form a unique fingerprint.

Cite this