Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axis
Abstract Background Previous studies have reported SIRT1 was inversely modulated by miR‐34a, However, mechanism of metformin (MFN)'s renal podocyte protection under high glucose (HG) conditions and the connection between miR‐34a and SIRT1 expression in diabetic nephropathy (DN) remain unclear....
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.1053 |
| _version_ | 1797346785189953536 |
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| author | Xudong Zhuang Zhuye Sun Huasheng Du Tianhui Zhou Jing Zou Wei Fu |
| author_facet | Xudong Zhuang Zhuye Sun Huasheng Du Tianhui Zhou Jing Zou Wei Fu |
| author_sort | Xudong Zhuang |
| collection | DOAJ |
| description | Abstract Background Previous studies have reported SIRT1 was inversely modulated by miR‐34a, However, mechanism of metformin (MFN)'s renal podocyte protection under high glucose (HG) conditions and the connection between miR‐34a and SIRT1 expression in diabetic nephropathy (DN) remain unclear. Method We aimed to further elucidate the role of miR‐34a in HG‐treated podocytes in DN. A conditionally immortalized human podocyte cell line was cultivated in d‐glucose (30 mM). Results Microarray and RT‐qPCR revealed that miR‐34a was downregulated in HG‐treated podocytes. Additionally, miR‐34a levels increased in MFN‐treated HG‐induced podocytes. CCK‐8 assay, colony formation assay, flow cytometry, and Western blot detection showed that HG treatment reduced cell viability and promoted via HG treatment, and MFN treatment reversed this phenotypic change. MiR‐34a upregulation caused restored cell viability and suppressed cell apoptosis in HG‐treated podocytes, and miR‐34a downregulation led to damaged cell survival and induced apoptosis in MFN‐administered and HG‐treated podocytes. The dual luciferase reporter assay showed that SIRT1 3′‐UTR was a direct miR‐34a target. Further studies demonstrated an elevation in SIRT1 levels in HG‐exposed podocytes, whereas MFN treatment decreased SIRT1 levels. In addition, miR‐34a upregulation led to reduced SIRT1 expression, whereas miR‐34a inhibition increased SIRT1 levels in cells. MFN‐induced miR‐34a suppresses podocyte apoptosis under HG conditions by acting on SIRT1. Conclusion This study proposes a promising approach to interpret the mechanisms of action of the MFN‐miR‐34a axis involved in DN. |
| first_indexed | 2024-03-08T11:38:01Z |
| format | Article |
| id | doaj.art-2005a7ff1c564851a43480dc0a276151 |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-03-08T11:38:01Z |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-2005a7ff1c564851a43480dc0a2761512024-01-25T11:02:19ZengWileyImmunity, Inflammation and Disease2050-45272024-01-01121n/an/a10.1002/iid3.1053Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axisXudong Zhuang0Zhuye Sun1Huasheng Du2Tianhui Zhou3Jing Zou4Wei Fu5Department of Dialysis Linyi Traditional Chinese Medicine Hospital Linyi Shandong ChinaDepartment of Pharmacy Rizhao Hospital of Traditional Chinese Medicine Rizhao Shandong ChinaDepartment of Nephrology Qingdao Municipal Hospital Qingdao Shandong ChinaBeijing University of Chinese Medicine Beijing ChinaDepartment of Dialysis Linyi Traditional Chinese Medicine Hospital Linyi Shandong ChinaDepartment of Drug Dispensing Zibo Central Hospital Zibo Shandong ChinaAbstract Background Previous studies have reported SIRT1 was inversely modulated by miR‐34a, However, mechanism of metformin (MFN)'s renal podocyte protection under high glucose (HG) conditions and the connection between miR‐34a and SIRT1 expression in diabetic nephropathy (DN) remain unclear. Method We aimed to further elucidate the role of miR‐34a in HG‐treated podocytes in DN. A conditionally immortalized human podocyte cell line was cultivated in d‐glucose (30 mM). Results Microarray and RT‐qPCR revealed that miR‐34a was downregulated in HG‐treated podocytes. Additionally, miR‐34a levels increased in MFN‐treated HG‐induced podocytes. CCK‐8 assay, colony formation assay, flow cytometry, and Western blot detection showed that HG treatment reduced cell viability and promoted via HG treatment, and MFN treatment reversed this phenotypic change. MiR‐34a upregulation caused restored cell viability and suppressed cell apoptosis in HG‐treated podocytes, and miR‐34a downregulation led to damaged cell survival and induced apoptosis in MFN‐administered and HG‐treated podocytes. The dual luciferase reporter assay showed that SIRT1 3′‐UTR was a direct miR‐34a target. Further studies demonstrated an elevation in SIRT1 levels in HG‐exposed podocytes, whereas MFN treatment decreased SIRT1 levels. In addition, miR‐34a upregulation led to reduced SIRT1 expression, whereas miR‐34a inhibition increased SIRT1 levels in cells. MFN‐induced miR‐34a suppresses podocyte apoptosis under HG conditions by acting on SIRT1. Conclusion This study proposes a promising approach to interpret the mechanisms of action of the MFN‐miR‐34a axis involved in DN.https://doi.org/10.1002/iid3.1053DNmetforminmiR‐34apodocyteSIRT1 |
| spellingShingle | Xudong Zhuang Zhuye Sun Huasheng Du Tianhui Zhou Jing Zou Wei Fu Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axis Immunity, Inflammation and Disease DN metformin miR‐34a podocyte SIRT1 |
| title | Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axis |
| title_full | Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axis |
| title_fullStr | Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axis |
| title_full_unstemmed | Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axis |
| title_short | Metformin inhibits high glucose‐induced apoptosis of renal podocyte through regulating miR‐34a/SIRT1 axis |
| title_sort | metformin inhibits high glucose induced apoptosis of renal podocyte through regulating mir 34a sirt1 axis |
| topic | DN metformin miR‐34a podocyte SIRT1 |
| url | https://doi.org/10.1002/iid3.1053 |
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