Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice

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dc.contributor.authorLeo, C.H.
dc.contributor.authorOu, J.L.M.
dc.contributor.authorOng, E.S.
dc.contributor.authorQin, C.X.
dc.contributor.authorRitchie, R.H.
dc.contributor.authorParry, L.J.
dc.contributor.authorNg, H.H.
dc.date.issued2023
dc.description.abstractBackground: The peptide hormone relaxin has potent anti-fibrotic and anti-inflammatory properties in various organs, including the kidneys. However, the protective effects of relaxin in the context of diabetic kidney complications remain controversial. Here, we aimed to evaluate the effects of relaxin treatment on key markers of kidney fibrosis, oxidative stress, and inflammation and their subsequent impact on bile acid metabolism in the streptozotocin-induced diabetes mouse model. Methods and results: Male mice were randomly allocated to placebo-treated control, placebo-treated diabetes or relaxin-treated diabetes groups (0.5 mg/kg/d, final 2 weeks of diabetes). After 12 weeks of diabetes or sham, the kidney cortex was harvested for metabolomic and gene expression analyses. Diabetic mice exhibited significant hyperglycaemia and increased circulating levels of creatine, hypoxanthine and trimethylamine N-oxide in the plasma. This was accompanied by increased expression of key markers of oxidative stress (Txnip), inflammation (Ccl2 and Il6) and fibrosis (Col1a1, Mmp2 and Fn1) in the diabetic kidney cortex. Relaxin treatment for the final 2 weeks of diabetes significantly reduced these key markers of renal fibrosis, inflammation, and oxidative stress in diabetic mice. Furthermore, relaxin treatment significantly increased the levels of bile acid metabolites, deoxycholic acid and sodium glycodeoxycholic acid, which may in part contribute to the renoprotective action of relaxin in diabetes. Conclusion: In summary, this study shows the therapeutic potential of relaxin and that it may be used as an adjunctive treatment for diabetic kidney complications.
dc.description.statementofresponsibilityChen Huei Leo, Jamie Li Min Ou, Eng Shi Ong, Cheng Xue Qin, Rebecca H. Ritchie, Laura J. Parry, Hooi Hooi Ng
dc.identifier.citationBiomedicine and Pharmacotherapy, 2023; 162:114578-1-114578-9
dc.identifier.doi10.1016/j.biopha.2023.114578
dc.identifier.issn0753-3322
dc.identifier.issn1950-6007
dc.identifier.orcidParry, L.J. [0000-0002-6883-3418]
dc.identifier.urihttps://hdl.handle.net/2440/140335
dc.language.isoen
dc.publisherElsevier BV
dc.relation.granthttp://purl.org/au-research/grants/arc/LP110200543
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1059660
dc.rights© 2023 The Author(s). Published by Elsevier Masson SAS. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
dc.source.urihttps://doi.org/10.1016/j.biopha.2023.114578
dc.subjectKidney
dc.subjectAnimals
dc.subjectMice
dc.subjectDiabetic Nephropathies
dc.subjectDiabetes Mellitus, Experimental
dc.subjectFibrosis
dc.subjectInflammation
dc.subjectStreptozocin
dc.subjectRelaxin
dc.subjectOxidative Stress
dc.subjectMale
dc.subject.meshKidney
dc.subject.meshAnimals
dc.subject.meshMice
dc.subject.meshDiabetic Nephropathies
dc.subject.meshDiabetes Mellitus, Experimental
dc.subject.meshFibrosis
dc.subject.meshInflammation
dc.subject.meshStreptozocin
dc.subject.meshRelaxin
dc.subject.meshOxidative Stress
dc.subject.meshMale
dc.titleRelaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice
dc.typeJournal article
pubs.publication-statusPublished

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