miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease
Background Diabetic kidney disease (DKD), characterized by mesangial fibrosis and renal dysfunction, is a major microvascular complication of diabetes. Studies have shown that miRNAs are closely related to the progression of DKD. Therefore, in this study, we aimed to explore whether miR-1225-3p can...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2025.2484632 |
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| author | Juntai Zhang Yan Cai Yan Qin Jie Liu Jie Ding Mengying Xu Li Yang Yuanxin Zheng Xi Zhang |
| author_facet | Juntai Zhang Yan Cai Yan Qin Jie Liu Jie Ding Mengying Xu Li Yang Yuanxin Zheng Xi Zhang |
| author_sort | Juntai Zhang |
| collection | DOAJ |
| description | Background Diabetic kidney disease (DKD), characterized by mesangial fibrosis and renal dysfunction, is a major microvascular complication of diabetes. Studies have shown that miRNAs are closely related to the progression of DKD. Therefore, in this study, we aimed to explore whether miR-1225-3p can regulate Smad ubiquitin regulatory factor 2 (SMURF2)-mediated carbohydrate response element binding protein (ChREBP) ubiquitination through Rho GTPase-activating protein 5 (ARHGAP5) to affect fibrosis in DKD.Methods DKD mice were established by intraperitoneally injecting streptozocin (STZ), and a DKD cell model was generated by culturing in media supplemented with 25 mmol/L glucose (high glucose, HG). StarBase was used to predict the target binding sites between miR-1225-3p and ARHGAP5, and a dual-luciferase reporter gene assay was used to verify this relationship. Western blotting, RT–qPCR, flow cytometry, immunoprecipitation, ELISAs, HE staining, and Masson staining were used to detect relevant indicators.Results ARHGAP5 and SMURF2 expression was decreased, but ChREBP was highly expressed in the renal tissue of DKD mice and HG-induced mouse mesangial cells (MMCs). miR-1225-3p could target and regulate the transcription of ARHGAP5, and an association between ARHGAP5 and SMURF2 was revealed. miR-1225-3p facilitated fibrosis and oxidative stress in MCCs by inhibiting ARHGAP5. In addition, SMURF2 promoted the ubiquitination of HA-ChREBP, and miR-1225-3p facilitated fibrosis and oxidative stress by mediating the ARHGAP5/SMURF2-mediated ubiquitination of ChREBP in MCCs. Furthermore, the miR-1225-3p inhibitor inhibited fibrosis and inflammation in the renal tissues of DKD mice.Conclusion miR-1225-3p facilitates fibrosis and oxidative stress by mediating ARHGAP5/SMURF2-mediated ubiquitination of ChREBP. |
| format | Article |
| id | doaj-art-72bde1b3ce6947d28d6f5d9f99b26ad7 |
| institution | DOAJ |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-72bde1b3ce6947d28d6f5d9f99b26ad72025-08-20T03:06:25ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2484632miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney diseaseJuntai Zhang0Yan Cai1Yan Qin2Jie Liu3Jie Ding4Mengying Xu5Li Yang6Yuanxin Zheng7Xi Zhang8Department of Nephrology & Immunology, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Nephrology, The Fifth Affiliated Hospital of Kunming Medical University, Gejiu, Yunnan, ChinaDepartment of Nephrology & Immunology, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Pathology, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Ultrasound, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Nephrology & Immunology, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Nephrology & Immunology, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Nephrology & Immunology, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Nephrology & Immunology, Affiliated Ganmei Hospital of Kunming Medical University, Kunming, Yunnan, ChinaBackground Diabetic kidney disease (DKD), characterized by mesangial fibrosis and renal dysfunction, is a major microvascular complication of diabetes. Studies have shown that miRNAs are closely related to the progression of DKD. Therefore, in this study, we aimed to explore whether miR-1225-3p can regulate Smad ubiquitin regulatory factor 2 (SMURF2)-mediated carbohydrate response element binding protein (ChREBP) ubiquitination through Rho GTPase-activating protein 5 (ARHGAP5) to affect fibrosis in DKD.Methods DKD mice were established by intraperitoneally injecting streptozocin (STZ), and a DKD cell model was generated by culturing in media supplemented with 25 mmol/L glucose (high glucose, HG). StarBase was used to predict the target binding sites between miR-1225-3p and ARHGAP5, and a dual-luciferase reporter gene assay was used to verify this relationship. Western blotting, RT–qPCR, flow cytometry, immunoprecipitation, ELISAs, HE staining, and Masson staining were used to detect relevant indicators.Results ARHGAP5 and SMURF2 expression was decreased, but ChREBP was highly expressed in the renal tissue of DKD mice and HG-induced mouse mesangial cells (MMCs). miR-1225-3p could target and regulate the transcription of ARHGAP5, and an association between ARHGAP5 and SMURF2 was revealed. miR-1225-3p facilitated fibrosis and oxidative stress in MCCs by inhibiting ARHGAP5. In addition, SMURF2 promoted the ubiquitination of HA-ChREBP, and miR-1225-3p facilitated fibrosis and oxidative stress by mediating the ARHGAP5/SMURF2-mediated ubiquitination of ChREBP in MCCs. Furthermore, the miR-1225-3p inhibitor inhibited fibrosis and inflammation in the renal tissues of DKD mice.Conclusion miR-1225-3p facilitates fibrosis and oxidative stress by mediating ARHGAP5/SMURF2-mediated ubiquitination of ChREBP.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2484632Diabetic kidney diseaserenal fibrosisChREBPARHGAP5miR-1225-3pSMURF2 |
| spellingShingle | Juntai Zhang Yan Cai Yan Qin Jie Liu Jie Ding Mengying Xu Li Yang Yuanxin Zheng Xi Zhang miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease Renal Failure Diabetic kidney disease renal fibrosis ChREBP ARHGAP5 miR-1225-3p SMURF2 |
| title | miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease |
| title_full | miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease |
| title_fullStr | miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease |
| title_full_unstemmed | miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease |
| title_short | miR-1225-3p regulates fibrosis in mesangial cells via SMURF2-mediated ubiquitination of ChREBP in diabetic kidney disease |
| title_sort | mir 1225 3p regulates fibrosis in mesangial cells via smurf2 mediated ubiquitination of chrebp in diabetic kidney disease |
| topic | Diabetic kidney disease renal fibrosis ChREBP ARHGAP5 miR-1225-3p SMURF2 |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2025.2484632 |
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