title: Metformin prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction.
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.
authors.affiliation: Department of Medicine/Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Cavaglieri
authors.affiliation: Department of Medicine/Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Day
authors.affiliation: Department of Medicine/Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA. Electronic address: feliers@uthscsa.edu.
authors.forename: Denis
authors.initials: D
authors.lastname: Feliers
authors.affiliation: Department of Medicine/Nephrology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Abboud
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis; D007684:Kidney Tubules / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D009395:Nephritis, Interstitial / Q000209:etiology / Q000517:prevention & control*; D014517:Ureteral Obstruction / Q000150:complications / Q000188:drug therapy*
chemical_list: D000893:Anti-Inflammatory Agents; D008687:Metformin; D000263:Adenylate Kinase
keywords: Adenosine monophosphate-activated kinase; Fibrosis; Inflammation; Kidney; Metformin