ArticleBritish journal of pharmacology2020
Connexin32 ameliorates renal fibrosis in diabetic mice by promoting K48-linked NADPH oxidase 4 polyubiquitination and degradation.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 30 citations in OpenAlex.
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Regulatory networks of post-translational modifications in diabetic kidney disease: from pathogenic mechanisms to therapeutic frontiers.Frontiers in endocrinology · 2026Review
- The E3 ubiquitin ligase TRIM39 modulates renal fibrosis induced by unilateral ureteral obstruction through regulating proteasomal degradation of PRDX3.Cell death discovery · 2024Article
- The role of intercellular communication in diabetic nephropathy.Frontiers in immunology · 2024Review
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Smurf1 Facilitates Oxidative Stress and Fibrosis of Ligamentum Flavum by Promoting Nrf2 Ubiquitination and Degradation.Mediators of inflammation · 2023Article
- Gentiopicroside targets PAQR3 to activate the PI3K/AKT signaling pathway and ameliorate disordered glucose and lipid metabolism.Acta pharmaceutica Sinica. B · 2022Article
- miR-154-5p Affects the TGFOxidative medicine and cellular longevity · 2022Article
- Connexin mRNA distribution in adult mouse kidneys.Pflugers Archiv : European journal of physiology · 2021Article
- FOXA1 Suppresses SATB1 Transcription and Inactivates the Wnt/β-Catenin Pathway to Alleviate Diabetic Nephropathy in a Mouse Model.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Connexin32 ameliorates renal fibrosis in diabetic mice by promoting K48-linked NADPH oxidase 4 polyubiquitination and degradation.British journal of pharmacology · 2020Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
background and purposeNox4 is the major isoform of NADPH oxidase found in the kidney and contributes to the pathogenesis of diabetic nephropathy. However, the molecular mechanisms of increased Nox4 expression induced by hyperglycaemia remain to be elucidated. Here, the role of the connexin32-Nox4 signalling axis in diabetic nephropathy and its related mechanisms were investigated. EXPERIMENTAL APPROACH: Diabetes was induced in mice by low-dose streptozotocin (STZ) combined with a high-fat diet. Effects of connexin32 on Nox4 expression and on renal function and fibrosis in STZ-induced diabetic mice were investigated using adenovirus-overexpressing connexin32 and connexin32-deficient mice. Interactions between connexin32 and Nox4 were analysed by co-immunoprecipitation and immunofluorescence assays. KEY
resultsConnexin32 was down-regulated in the kidneys of STZ-induced diabetic mice. Overexpression of connexin32 reduced expression of Nox4 and improved renal function and fibrosis in diabetic mice, whereas connexin32 deficiency had opposite effects. Down-regulation of fibronectin expression by connexin32 was not dependent on gap junctional intercellular communication involving connexin32. Connexin32 interacted with Nox4 and reduced the generation of hydrogen peroxide, leading to the down-regulation of fibronectin expression. Mechanistically, connexin32 decreased Nox4 expression by promoting its K48-linked polyubiquitination. Interestingly, Smurf1 overexpression inhibited K48-linked polyubiquitination of Nox4. Furthermore, connexin32 interacted with Smurf1 and inhibited its expression. CONCLUSION AND IMPLICATIONS: Connexin32 ameliorated renal fibrosis in diabetic mice by promoting K48-linked Nox4 polyubiquitination and degradation via inhibition of Smurf1 expression. Targeting the connexin32-Nox4 signalling axis may contribute to the development of novel treatments for diabetic nephropathy.
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