Please use this identifier to cite or link to this item:
Title: Mutation of regulatory phosphorylation sites in PFKFB2 does not affect the anti-fibrotic effect of metformin in the kidney.
Austin Authors: Harley, Geoff ;Katerelos, Marina ;Gleich, Kurt;Lee, Mardiana ;Mount, Peter F ;Power, David A 
Affiliation: Nephrology
Medicine (University of Melbourne)
Issue Date: 2023 2023
Publication information: PloS one 2023; 18(2):e0280792
Abstract: The anti-fibrotic effect of metformin has been widely demonstrated. Fibrosis in the kidney after injury is associated with reduced expression of genes involved in both fatty acid and glycolytic energy metabolism. We have previously reported that the anti-fibrotic effect of metformin requires phosphoregulation of fatty acid oxidation by AMP-activated protein kinase (AMPK). To determine whether metformin also acts via regulation of glycolysis, we mutated regulatory phosphosites in the PFKFB2 isoform of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB2), a key regulator of glycolysis in the kidney. Mice with inactivating knockin (KI) mutations of the phosphorylation sites in PFKFB2 (PFKFB2 KI mice), which reduces the ability to increase the rate of glycolysis following stimulation, were used. Metformin was administered via drinking water to mice with a unilateral ureteric obstruction (UUO) model of renal fibrosis. In the PFKFB2 KI mice treated with metformin, there was decreased fibrosis and macrophage infiltration following UUO as assessed by Western blot for fibronectin and RT-PCR for α-smooth muscle actin, collagen 3, and F4.80, and confirmed by histology. Expression of the inducible PFKFB3 isoform was increased with metformin in UUO in both WT and PFKFB2 KI mice. There was no significant difference between WT and PFKFB2 KI mice treated with metformin in the degree of fibrosis following UUO in any of the Western blot or RT-PCR parameters that were measured. These data show that inhibition of the regulation of glycolysis by PFKFB2 does not diminish the anti-fibrotic effect of metformin in a model of renal fibrosis.
DOI: 10.1371/journal.pone.0280792
ORCID: 0000-0001-6992-5392
Journal: PloS one
Start page: e0280792
PubMed URL: 36757995
ISSN: 1932-6203
Type: Journal Article
Subjects: Metformin/pharmacology
Kidney Diseases/drug therapy
Kidney Diseases/genetics
Kidney Diseases/complications
Ureteral Obstruction/complications
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Mar 30, 2023

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.