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Tissue-specific effects of targeted mutation of Mir29b1 in rats. EBioMedicine 2018 Sep;35:260-269

Date

08/19/2018

Pubmed ID

30120082

Pubmed Central ID

PMC6156712

DOI

10.1016/j.ebiom.2018.08.016

Scopus ID

2-s2.0-85051562841

Abstract

BACKGROUND: miR-29 is a master regulator of extracellular matrix genes, but conflicting data on its anti-fibrotic effect have been reported. miR-29 improves nitric oxide (NO) production in arterioles by targeting Lypla1. Mir29b1 targeted mutation exacerbates hypertension in a model derived from the Dahl salt-sensitive rat. We examined the effect of Mir29b1 mutation on tissue fibrosis and NO levels with a focus on kidney regions.

METHODS: Mir29b1 targeted mutant rats on the genetic background of SS-Chr13BN rats were studied. Masson trichrome staining, molecular and biochemical assays, metabolic cage studies, and bioinformatic analysis of human genomic data were performed.

FINDINGS: The abundance of miR-29b and the co-transcribed miR-29a was substantially lower in mutant rats. Tissue fibrosis was significantly increased in the renal outer medulla, but not in the renal cortex, heart or liver in mutant rats on a 0.4% NaCl diet. Lypla1 protein abundance was significantly higher and NO levels lower in the renal outer medulla, but not in the renal cortex. After 14 days of a 4% NaCl diet, 24 h urine volume and urinary sodium excretion was significantly lower in mutant rats, and tissue fibrosis became higher in the heart. NO levels were lower in the renal outer medulla and heart, but not in the renal cortex. Human miR-29 genes are located in proximity with blood pressure-associated single nucleotide polymorphisms.

INTERPRETATION: The renal outer medulla might be particularly susceptible to the injurious effects of a miR-29 insufficiency, which might contribute to the development of hypertension in Mir29b1 mutant rats.

Author List

Xue H, Zhang G, Geurts AM, Usa K, Jensen DM, Liu Y, Widlansky ME, Liang M

Authors

Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin
David Jensen in the CTSI department at Medical College of Wisconsin - CTSI
Mingyu Liang PhD Center Director, Professor in the Physiology department at Medical College of Wisconsin
Yong Liu PhD Assistant Professor in the Physiology department at Medical College of Wisconsin
Michael E. Widlansky MD Associate Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Blood Pressure
Fibrosis
Humans
Kidney
Liver
Male
MicroRNAs
Mutation
Myocardium
Nitric Oxide
Nitrites
Organ Specificity
Polymorphism, Single Nucleotide
Rats
Sodium
Thiolester Hydrolases
Transcription, Genetic
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d