ArticleCell communication and signaling : CCS2023
Targeting Src homology phosphatase 2 ameliorates mouse diabetic nephropathy by attenuating ERK/NF-κB pathway-mediated renal inflammation.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- The role of classical protein tyrosine phosphatases in diabetic kidney disease and therapeutic implications.Journal of biomedical science · 2026Review
- SHP2 improves ovarian morphology and steroidogenic function in a rat PCOS model by modulating IRE1α/XBP1/NLRP3-mediated granulosa cell pyroptosis.Scientific reports · 2026Article
- Screening and analysis of malt pentapeptide DPP-IV inhibitory activity.NPJ science of food · 2025Article
- NF-κB p65 mediated lnc-Traf3ip2 exacerbates renal fibrosis in diabetic kidney disease.Acta diabetologica · 2025Article
- Interplay Between the Mineralocorticoid System, Inflammation, Hypertension, and Kidney Disease.Kidney360 · 2025Review
- Knockdown of SHP-2 delays renal tubular epithelial cell injury in diabetic nephropathy by inhibiting NLRP3 inflammasome-mediated pyroptosis.Open life sciences · 2025Article
- Article
- Correlation between serum autotaxin levels and optic neuropathy in early diabetic retinopathy: a case-control study.Frontiers in medicine · 2025Article
- Fiery Connections: Macrophage-Mediated Inflammation, the Journey from Obesity to Type 2 Diabetes Mellitus and Diabetic Kidney Disease.Biomedicines · 2024Review
- Extracellular signal-regulated kinase is activated in podocytes from patients with diabetic nephropathy.Human cell · 2024Article
- Progress on the Anti-Inflammatory Activity and Structure-Efficacy Relationship of Polysaccharides from Medical and Edible Homologous Traditional Chinese Medicines.Molecules (Basel, Switzerland) · 2024Review
- [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
- Efficacy of Trametinib in Alleviating Cisplatin-Induced Acute Kidney Injury: Inhibition of Inflammation, Oxidative Stress, and Tubular Cell Death in a Mouse Model.Molecules (Basel, Switzerland) · 2024Article
- Emerging Role of SH3BP2 as Regulator of Immune and Nonimmune Cells in Nephrotic Syndrome.Glomerular diseasesReview
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal inflammation is a pivotal mechanism underlying the pathophysiology of diabetic nephropathy (DN). The Src homology phosphatase 2 (SHP2) has been demonstrated to be linked to diabetes-induced inflammation, yet its roles and explicit molecular mechanisms in DN remain unexplored. Here, we report that SHP2 activity is upregulated in both DN patients and db/db mice. In addition, pharmacological inhibition of SHP2 with its specific inhibitor PHPS1 alleviates DN in db/db mice and attenuates renal inflammation. In vitro, PHPS1 administration prevents inflammatory responses in HK-2 cells stimulated by high glucose (HG). Mechanistically, PHPS1 represses HG-induced activation of the proinflammatory ERK/NF-κB signaling pathway, and these inhibitory effects are blocked in the presence of an ERK specific inhibitor, hence demonstrating that PHPS1 suppresses ERK/NF-κB pathway-mediated inflammation. Moreover, PHPS1 retards ERK/NF-κB pathway activation in db/db mice, and histologically, SHP2 activity is positively correlated with ERK/NF-κB activation in DN patients. Taken together, these findings identify SHP2 as a potential therapeutic target and show that its pharmacological inhibition might be a promising strategy to mitigate DN. Video Abstract.
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