SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experiments
Abstract Background Dysfunction in podocyte mitophagy has been identified as a contributing factor to the onset and progression of diabetic nephropathy (DN), and BMAL1 plays an important role in the regulation of mitophagy. Thus, this study intended to examine the impact of BMAL1 on podocyte mitopha...
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2025-01-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02280-5 |
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| author | Yanxia Rui Yinfeng Guo Linying He Min-er Wang Henglan Wu |
| author_facet | Yanxia Rui Yinfeng Guo Linying He Min-er Wang Henglan Wu |
| author_sort | Yanxia Rui |
| collection | DOAJ |
| description | Abstract Background Dysfunction in podocyte mitophagy has been identified as a contributing factor to the onset and progression of diabetic nephropathy (DN), and BMAL1 plays an important role in the regulation of mitophagy. Thus, this study intended to examine the impact of BMAL1 on podocyte mitophagy in DN and elucidate its underlying mechanisms. Materials and methods High D-glucose (HG)-treated MPC5 cells was used as a podocyte injury model for investigating the potential roles of BMAL1 in DN. Mitophagy was examined by detecting autophagosomes using transmission electron microscopy, and detecting the colocalization of LC3 and Tom20 using immunofluorescence staining. The interaction between BMAL1 and SIRT1 was conducted by immunoprecipitation (Co-IP) assay. Results In HG-induced podocyte injury model, we found that BMAL1 and SIRT1 mRNA level was significantly decreased, and positively correlated with mitophagy dysfunction. BMAL1 overexpression could ameliorate HG-induced podocyte injury, evidenced by improved cell viability, decreased cell apoptosis and inflammatory cytokines expression (TNF-α, IL-1β, and IL-6). BMAL1 overexpression could promote podocyte mitophagy coupled with increased expression of mitophagy markers PINK1 and Parkin. In terms of mechanism, Co-IP suggested that BMAL1 could interact with SIRT1. SIRT1 inhibitor Ex-527 addition obviously inhibit the effect of BMAL1 overexpression on the mitophagy, demonstrating that BMAL1 may act on mitophagy by SIRT1//PGC-1α axis. Conclusions Our in vitro experiments demonstrate that BMAL1/SIRT1/PGC-1α pathway may protect podocytes against HG-induced DN through promoting mitophagy. |
| format | Article |
| id | doaj-art-1eb37828fb604a3ea26166091d927993 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-1eb37828fb604a3ea26166091d9279932025-01-19T12:14:53ZengBMCEuropean Journal of Medical Research2047-783X2025-01-0130111210.1186/s40001-025-02280-5SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experimentsYanxia Rui0Yinfeng Guo1Linying He2Min-er Wang3Henglan Wu4Department of Nephrology, Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing)Department of Nephrology, Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing)Jiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical UniversityJiaxing University Master Degree Cultivation Base, Zhejiang Chinese Medical UniversityDepartment of Nephrology, Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing)Abstract Background Dysfunction in podocyte mitophagy has been identified as a contributing factor to the onset and progression of diabetic nephropathy (DN), and BMAL1 plays an important role in the regulation of mitophagy. Thus, this study intended to examine the impact of BMAL1 on podocyte mitophagy in DN and elucidate its underlying mechanisms. Materials and methods High D-glucose (HG)-treated MPC5 cells was used as a podocyte injury model for investigating the potential roles of BMAL1 in DN. Mitophagy was examined by detecting autophagosomes using transmission electron microscopy, and detecting the colocalization of LC3 and Tom20 using immunofluorescence staining. The interaction between BMAL1 and SIRT1 was conducted by immunoprecipitation (Co-IP) assay. Results In HG-induced podocyte injury model, we found that BMAL1 and SIRT1 mRNA level was significantly decreased, and positively correlated with mitophagy dysfunction. BMAL1 overexpression could ameliorate HG-induced podocyte injury, evidenced by improved cell viability, decreased cell apoptosis and inflammatory cytokines expression (TNF-α, IL-1β, and IL-6). BMAL1 overexpression could promote podocyte mitophagy coupled with increased expression of mitophagy markers PINK1 and Parkin. In terms of mechanism, Co-IP suggested that BMAL1 could interact with SIRT1. SIRT1 inhibitor Ex-527 addition obviously inhibit the effect of BMAL1 overexpression on the mitophagy, demonstrating that BMAL1 may act on mitophagy by SIRT1//PGC-1α axis. Conclusions Our in vitro experiments demonstrate that BMAL1/SIRT1/PGC-1α pathway may protect podocytes against HG-induced DN through promoting mitophagy.https://doi.org/10.1186/s40001-025-02280-5BMAL1MitophagySIRT1/PGC-1αDiabetic nephropathyPodocyte injury |
| spellingShingle | Yanxia Rui Yinfeng Guo Linying He Min-er Wang Henglan Wu SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experiments European Journal of Medical Research BMAL1 Mitophagy SIRT1/PGC-1α Diabetic nephropathy Podocyte injury |
| title | SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experiments |
| title_full | SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experiments |
| title_fullStr | SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experiments |
| title_full_unstemmed | SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experiments |
| title_short | SIRT1/PGC-1α-mediated mitophagy participates the improvement roles of BMAL1 in podocytes injury in diabetic nephropathy: evidences from in vitro experiments |
| title_sort | sirt1 pgc 1α mediated mitophagy participates the improvement roles of bmal1 in podocytes injury in diabetic nephropathy evidences from in vitro experiments |
| topic | BMAL1 Mitophagy SIRT1/PGC-1α Diabetic nephropathy Podocyte injury |
| url | https://doi.org/10.1186/s40001-025-02280-5 |
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