ArticleExperimental & molecular medicine2022
Pan-Src kinase inhibitor treatment attenuates diabetic kidney injury via inhibition of Fyn kinase-mediated endoplasmic reticulum stress.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 33 citations in OpenAlex.
- Imbalance of mitochondria and abnormalities in lipid metabolism in Diabetic Tubulopathy.Annals of medicine · 2026Review
- Material Basis and Mechanisms of Action of PuRenDan in the Treatment of Type 2 Diabetes Mellitus: An Integrated Network Pharmacology and Molecular Simulation Study.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The Role of Keratin in the Mechanisms of Kidney Diseases.BioMed research international · 2026Review
- Intermodulation of endoplasmic reticulum stress and ferroptosis in diabetic nephropathy: molecular mechanisms and therapeutic potentials.Apoptosis : an international journal on programmed cell death · 2025Review
- FAK-dependent activation of src family kinase member BLK contributed to endometrial fibrosis via endoplasmic reticulum stress.Cell & bioscience · 2025Article
- Network Pharmacology, Molecular Docking and Molecular Dynamics Studies to Predict the Molecular Targets and Mechanisms of Action ofPlants (Basel, Switzerland) · 2025Article
- Machine learning-based transcriptomic analysis identifies candidate genes in sepsis-induced coagulopathy and explores the immunomodulatory potential of baicalein.Human genomics · 2025Article
- Fyn Kinase: A Potential Target in Glucolipid Metabolism and Diabetes Mellitus.Current issues in molecular biology · 2025Review
- Shenfushu granules attenuate diabetic kidney disease by inhibitingWorld journal of diabetes · 2025Article
- The status of studies on the mechanism of microcirculatory dysfunction in the process of diabetic kidney injury.Diabetology & metabolic syndrome · 2025Review
- Investigating potential targets of Wulingsan in diabetic nephropathy through network pharmacology and experimental validation.Frontiers in molecular biosciences · 2025Article
- Investigation of the Potential Pharmacological Substance Basis and Mechanism of Action of Xuantu Granules in Treating Diabetic Kidney Disease Based on UHPLC-Q-Exactive-HRMS and Bioinformatics.Combinatorial chemistry & high throughput screening · 2025Article
- Hck promotes IL-1β-induced extracellular matrix degradation, inflammation, and apoptosis in osteoarthritis via activation of the JAK-STAT3 signaling pathway.Advances in rheumatology (London, England) · 2024Article
- [Euonymus alatus delays progression of diabetic kidney disease in mice by regulating EGFR tyrosine kinase inhibitor resistance signaling pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Fibrosis in Chronic Kidney Disease: Pathophysiology and Therapeutic Targets.Journal of clinical medicine · 2024Review
- Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.Frontiers in pharmacology · 2024Review
- Research progress on endoplasmic reticulum homeostasis in kidney diseases.Cell death & disease · 2023Review
- An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway.Journal of translational medicine · 2023Article
- Podocarpusflavone alleviated renal fibrosis in obstructive nephropathy by inhibiting Fyn/Stat3 signaling pathway.Journal of natural medicines · 2023Article
- Review
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7 authors at 2 institutions in 1 country.
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Abstract
Src family kinases (SFKs) have been implicated in the pathogenesis of kidney fibrosis. However, the specific mechanism by which SFKs contribute to the progression of diabetic kidney disease (DKD) remains unclear. Our preliminary transcriptome analysis suggested that SFK expression was increased in diabetic kidneys and that the expression of Fyn (a member of the SFKs), along with genes related to unfolded protein responses from the endoplasmic reticulum (ER) stress signaling pathway, was upregulated in the tubules of human diabetic kidneys. Thus, we examined whether SFK-induced ER stress is associated with DKD progression. Mouse proximal tubular (mProx24) cells were transfected with Fyn or Lyn siRNA and exposed to high glucose and palmitate (HG-Pal). Streptozotocin-induced diabetic rats were treated with KF-1607, a novel pan-Src kinase inhibitor (SKI) with low toxicity. The effect of KF-1607 was compared to that of losartan, a standard treatment for patients with DKD. Among the SFK family members, the Fyn and Lyn kinases were upregulated under diabetic stress. HG-Pal induced p70S6 kinase and JNK/CHOP signaling and promoted tubular injury. Fyn knockdown but not Lyn knockdown inhibited this detrimental signaling pathway. In addition, diabetic rats treated with KF-1607 showed improved kidney function and decreased ER stress, inflammation, and fibrosis compared with those treated with losartan. Collectively, these findings indicate that Fyn kinase is a specific member of the SFKs implicated in ER stress activation leading to proximal tubular injury in the diabetic milieu and that pan-SKI treatment attenuates kidney injury in diabetic rats. These data highlight Fyn kinase as a viable target for the development of therapeutic agents for DKD.
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