ArticleActa pharmacologica Sinica2015
Blocking VEGF/Caveolin-1 signaling contributes to renal protection of fasudil in streptozotocin-induced diabetic rats.
Article in Acta pharmacologica Sinica, 2015. 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, 19 citations in OpenAlex.
- FTZ alleviates lipid deposition in diabetic kidney disease by AMPK/ACC/SREBP signaling pathway.Acta diabetologica · 2025Article
- The kidney antifibrotic effects of 5,7,3',4',5'-pentamethoxyflavone fromPharmaceutical biology · 2023Article
- Kirenol alleviates diabetic nephropathy via regulating TGF-β/Smads and the NF-κB signal pathway.Pharmaceutical biology · 2022Article
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
- Caveolin-1 Regulates Cellular Metabolism: A Potential Therapeutic Target in Kidney Disease.Frontiers in pharmacology · 2021Review
- Kidney-targeted baicalin-lysozyme conjugate ameliorates renal fibrosis in rats with diabetic nephropathy induced by streptozotocin.BMC nephrology · 2020Article
- Caveolin as a Novel Potential Therapeutic Target in Cardiac and Vascular Diseases: A Mini Review.Aging and disease · 2020Review
- Overview of Crosstalk Between Multiple Factor of Transcytosis in Blood Brain Barrier.Frontiers in neuroscience · 2019Review
- Caveolin-1 in the Pathogenesis of Diabetic Nephropathy: Potential Therapeutic Target?Current diabetes reports · 2017Review
- Intestinal Metrnl released into the gut lumen acts as a local regulator for gut antimicrobial peptides.Acta pharmacologica Sinica · 2016Article
- Effect of fosinopril on chemerin and VEGF expression in diabetic nephropathy rats.International journal of clinical and experimental pathology · 2015Article
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5 authors at 2 institutions in 1 country.
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Abstract
aimRhoA/ROCK signaling plays an important role in diabetic nephropathy, and ROCK inhibitor fasudil exerts nephroprotection in experimental diabetic nephropathy. In this study we investigated the molecular mechanisms underlying the protective actions of fasudil in a rat model of diabetic nephropathy.
methodsStreptozotocin (STZ)-induced diabetic rats, to which fasudil or a positive control drug enalapril were orally administered for 8 months. Metabolic parameters and blood pressure were assessed during the treatments. After the rats were euthanized, kidney samples were collected for histological and molecular biological studies. VEGF, VEGFR1, VEGFR2 and fibronectin expression, and Src and caveolin-1 phosphorylation in the kidneys were assessed using RT-PCR, Western blot and immunohistochemistry assays. The association between VEGFR2 and caveolin-1 was analyzed with immunoprecipitation.
resultsChronic administration of fasudil (30 and 100 mg·kg(-1)·d(-1)) or enalapril (10 mg/kg, bid) significantly attenuated the glomerular sclerosis and albuminuria in the diabetic rats. Furthermore, fasudil treatment prevented the upregulation of VEGF, VEGFR1, VEGFR2 and fibronectin, and the increased association between VEGFR2 and caveolin-1 in the renal cortices, and partially blocked Src activation and caveolin-1 phosphorylation on tyrosine 14 in the kidneys, whereas enalapril treatment had no effects on the VEGFR2/Src/caveolin-1 signaling pathway.
conclusionFasudil exerts protective actions in STZ-induced diabetic nephropathy by blocking the VEGFR2/Src/caveolin-1 signaling pathway and fibronectin upregulation. Thus, VEGFR2 may be a potential therapeutic target for the treatment of diabetic nephropathy.
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