ArticleFrontiers in endocrinology2022
An integrated RNA sequencing and network pharmacology approach reveals the molecular mechanism of dapagliflozin in the treatment of diabetic nephropathy.
Article in Frontiers in endocrinology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 34 citations in OpenAlex.
- Investigating the Effects and Potential Mechanisms of Astragalus Root Against Diabetic Nephropathy Based on Bioinformatics Analysis and In Vitro Validation.International journal of molecular sciences · 2026Article
- Non-Coding RNA in Type 2 Diabetes Cardio-Renal Complications and SGLT2 Inhibitor Response.International journal of molecular sciences · 2025Review
- Cardiometabolic Therapies Shape Non-Coding RNA Landscapes in Cardiovascular Fibrosis.Metabolites · 2025Review
- Association between composite dietary antioxidant index and increased urinary albumin excretion: a population-based study.Frontiers in nutrition · 2025Article
- Depression of LncRNA DANCR alleviates tubular injury in diabetic nephropathy by regulating KLF5 through sponge miR-214-5p.BMC nephrology · 2024Article
- Effect of dapagliflozin on proteomics and metabolomics of serum from patients with type 2 diabetes.Diabetology & metabolic syndrome · 2023Article
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Authors and funding
10 authors at 4 institutions in 1 country.
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Abstract
Dapagliflozin, an inhibitor of sodium-glucose cotransporter 2 (SGLT2), is a new type of oral hypoglycemic drugs which can promote glucose excretion in the kidney. Studies have shown that dapagliflozin has renoprotective effect in the treatment of type 2 diabetes. However, the underlying mechanism remains unclear. Here, we combined integrated RNA sequencing and network pharmacology approach to investigate the molecular mechanism of dapagliflozin for diabetic nephropathy (DN). Dapagliflozin significantly relieved glucose intolerance, urinary albumin/creatinine ratio (UACR) and renal pathological injuries of db/db mice. The LncRNA and mRNA expression in kidney tissues from control group (CR), db/db group (DN) and dapagliflozin group (DG) were assessed by RNA sequencing. We identified 7 LncRNAs and 64 mRNAs common differentially expressed in CR vs DN and DN vs DG, which were used to construct co-expression network to reveal significantly correlated expression patterns in DN. In addition, network pharmacology was used to predict the therapeutic targets of dapagliflozin and we constructed component-target-pathway network according to the results of RNA sequencing and network pharmacology. We found that SMAD9, PPARG, CD36, CYP4A12A, CYP4A12B, CASP3, H2-DMB2, MAPK1, MAPK3, C3 and IL-10 might be the pivotal targets of dapagliflozin for treating DN and these genes were mainly enriched in pathways including TGF-β signaling pathway, PPAR signaling pathway, Chemokine signaling pathway, etc. Our results have important implication and provide novel insights into the protective mechanism of dapagliflozin for treating DN.
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