Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/32139
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dc.contributor.authorHarley, Geoff-
dc.contributor.authorKaterelos, Marina-
dc.contributor.authorGleich, Kurt-
dc.contributor.authorLee, Mardiana-
dc.contributor.authorMount, Peter F-
dc.contributor.authorPower, David A-
dc.date2023-
dc.date.accessioned2023-02-14T04:27:38Z-
dc.date.available2023-02-14T04:27:38Z-
dc.date.issued2023-
dc.identifier.citationPloS one 2023; 18(2):e0280792en_US
dc.identifier.issn1932-6203-
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/32139-
dc.descriptionThis article originates from research conducted in the Kidney Lab, supported by the 2019-2021 NHMRC Grant awarded to David Power and administered by IBAS. In accordance with the IBAS Administration Officer's directive on November 6, 2023, this publication underwent validation under IBAS.en_US
dc.description.abstractThe 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.en_US
dc.language.isoeng-
dc.titleMutation of regulatory phosphorylation sites in PFKFB2 does not affect the anti-fibrotic effect of metformin in the kidney.en_US
dc.typeJournal Articleen_US
dc.identifier.journaltitlePloS oneen_US
dc.identifier.affiliationNephrologyen_US
dc.identifier.affiliationMedicine (University of Melbourne)en_US
dc.identifier.affiliationInstitute for Breathing and Sleepen_US
dc.identifier.doi10.1371/journal.pone.0280792en_US
dc.type.contentTexten_US
dc.identifier.orcid0000-0001-6992-5392en_US
dc.identifier.pubmedid36757995-
dc.description.volume18-
dc.description.issue2-
dc.description.startpagee0280792-
dc.subject.meshtermssecondaryMetformin/pharmacology-
dc.subject.meshtermssecondaryMetformin/metabolism-
dc.subject.meshtermssecondaryKidney/pathology-
dc.subject.meshtermssecondaryKidney Diseases/drug therapy-
dc.subject.meshtermssecondaryKidney Diseases/genetics-
dc.subject.meshtermssecondaryKidney Diseases/complications-
dc.subject.meshtermssecondaryUreteral Obstruction/complications-
local.name.researcherHarley, Geoff
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.fulltextNo Fulltext-
item.grantfulltextnone-
item.languageiso639-1en-
item.openairetypeJournal Article-
crisitem.author.deptNephrology-
crisitem.author.deptInstitute for Breathing and Sleep-
crisitem.author.deptNephrology-
crisitem.author.deptNephrology-
crisitem.author.deptInstitute for Breathing and Sleep-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptMedicine (University of Melbourne)-
crisitem.author.deptInstitute for Breathing and Sleep-
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