Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice
Background: 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 relax...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-06-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223003669 |
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| author | Chen Huei Leo Jamie Li Min Ou Eng Shi Ong Cheng Xue Qin Rebecca H. Ritchie Laura J. Parry Hooi Hooi Ng |
| author_facet | Chen Huei Leo Jamie Li Min Ou Eng Shi Ong Cheng Xue Qin Rebecca H. Ritchie Laura J. Parry Hooi Hooi Ng |
| author_sort | Chen Huei Leo |
| collection | DOAJ |
| description | Background: 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. |
| first_indexed | 2024-04-09T15:21:29Z |
| format | Article |
| id | doaj.art-f20db91d68974d309d3eb873b03c8659 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T15:21:29Z |
| publishDate | 2023-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-f20db91d68974d309d3eb873b03c86592023-04-29T14:45:52ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-06-01162114578Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic miceChen Huei Leo0Jamie Li Min Ou1Eng Shi Ong2Cheng Xue Qin3Rebecca H. Ritchie4Laura J. Parry5Hooi Hooi Ng6Science, Math & Technology, Singapore University of Technology & Design, Singapore; School of Biosciences, The University of Melbourne, Parkville, VIC, Australia; Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, AustraliaScience, Math & Technology, Singapore University of Technology & Design, SingaporeScience, Math & Technology, Singapore University of Technology & Design, SingaporeDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia; Baker Heart & Diabetes Institute, Melbourne, VIC, AustraliaDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia; Baker Heart & Diabetes Institute, Melbourne, VIC, AustraliaSchool of Biosciences, The University of Melbourne, Parkville, VIC, Australia; School of Biological Sciences, The University of Adelaide, Adelaide, SA, AustraliaSchool of Biosciences, The University of Melbourne, Parkville, VIC, Australia; Baker Heart & Diabetes Institute, Melbourne, VIC, Australia; Kolling Institute, Faculty of Medicine and Health, The University of Sydney and the Northern Sydney Local Health District, Sydney, NSW, Australia; Correspondence to: Royal North Shore Hospital, Level 12, Kolling Building, St. Leonards, NSW 2065, Australia.Background: 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.http://www.sciencedirect.com/science/article/pii/S0753332223003669Bile acidDiabetic kidney diseaseFibrosisInflammationOxidative stressRelaxin |
| spellingShingle | Chen Huei Leo Jamie Li Min Ou Eng Shi Ong Cheng Xue Qin Rebecca H. Ritchie Laura J. Parry Hooi Hooi Ng Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice Biomedicine & Pharmacotherapy Bile acid Diabetic kidney disease Fibrosis Inflammation Oxidative stress Relaxin |
| title | Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice |
| title_full | Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice |
| title_fullStr | Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice |
| title_full_unstemmed | Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice |
| title_short | Relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin-induced diabetic mice |
| title_sort | relaxin elicits renoprotective actions accompanied by increasing bile acid levels in streptozotocin induced diabetic mice |
| topic | Bile acid Diabetic kidney disease Fibrosis Inflammation Oxidative stress Relaxin |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223003669 |
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