Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cells Article Swipe
ShengZhe Yan
,
Ming‐Jiu Luo
,
Rui Zhou
,
Fenfen Peng
,
Meihua Zhang
,
Yujie Feng
,
Liang Zhao
,
Li Yang
,
Yanzhen Cheng
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s12967-025-06788-6
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1186/s12967-025-06788-6
Context Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown to ameliorate renal fibrosis in diabetic kidney disease (DKD), but the mechanism has not been fully explored. Methods The single-cell sequencing (scRNA-seq) data were downloaded from the Gene Expression Omnibus (GEO) database, and we selected the tissue data from db/m mice, db/db mice and db/db mice with SGLT2i treatment. The results were also validated by immunofluorescent staining and western blot in vivo and in vitro, respectively. Results Our study demonstrates that SGLT2i directly ameliorated fibrosis of proximal tubular cells by downregulating 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) expression in S1 proximal tubular segment cells (PT_S1) and decreasing the number of proximal tubular cell cluster with B-cell translocation gene 2 (Btg2) highly expressed (Btg2_PT). In addition, SGLT2i could indirectly influence macrophages through cell-cell communication between epithelial cells and macrophages, specifically via the App-CD74 ligand-receptor pair, thus suppressing the inflammatory response in macrophages, ultimately contributing to the delay in DKD progression. Conclusion Our study found that Hmgcs2 and Btg2 are therapeutic targets for Sodium-glucose cotransporter 2 inhibitors to ameliorate kidney fibrosis in diabetic kidney disease. Single-cell sequencing technology provided a high resolution of this study at the cellular level.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1186/s12967-025-06788-6
- https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-025-06788-6
- OA Status
- gold
- References
- 78
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413601103
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4413601103Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1186/s12967-025-06788-6Digital Object Identifier
- Title
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Sodium-glucose cotransporter 2 inhibitors alleviate renal fibrosis in diabetic kidney disease by inhibiting Hmgcs2 and Btg2 in proximal tubular cellsWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-08-25Full publication date if available
- Authors
-
ShengZhe Yan, Ming‐Jiu Luo, Rui Zhou, Fenfen Peng, Meihua Zhang, Yujie Feng, Liang Zhao, Li Yang, Yanzhen ChengList of authors in order
- Landing page
-
https://doi.org/10.1186/s12967-025-06788-6Publisher landing page
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https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-025-06788-6Direct link to full text PDF
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
- OA URL
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https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-025-06788-6Direct OA link when available
- Concepts
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Fibrosis, Cancer research, Kidney, In vivo, Cell, Kidney disease, Cotransporter, Endocrinology, Diabetes mellitus, Medicine, Chemistry, Internal medicine, Biology, Biochemistry, Sodium, Biotechnology, Organic chemistryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
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78Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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