ArticleActa pharmacologica Sinica2022
Epac activation ameliorates tubulointerstitial inflammation in diabetic nephropathy.
Article in Acta pharmacologica Sinica, 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, 31 citations in OpenAlex.
- Bufalin post-transcriptionally suppresses STAT3 to alleviate renal ferroptosis and tubulointerstitial fibrosis in diabetic kidney disease.Renal failure · 2026Article
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Shenlian (SL) Decoction Treat Diabetic Nephropathy by Regulating M1 Polarization of Macrophages and Pyroptosis of Renal Tubular Epithelial Cells.Journal of diabetes research · 2026Article
- Immune Cell Infiltration and Kynurenine Pathway Activation Define Early Injury and Progression in Diabetic Nephropathy.International journal of biological sciences · 2026Article
- CD248, targeted by veratramine and neobavaisoflavone, mediates pathological changes of renal tubular epithelial cells induced by high glucose.Hereditas · 2025Article
- Article
- EphrinB2 alleviates tubulointerstitial fibrosis in diabetic kidney disease.Journal of translational medicine · 2025Article
- Epac1 Inhibits Orbital Fibroblast Activation to Ameliorate Thyroid-Associated Orbitopathy-Like Features Through the JAK/STAT Signaling Pathway.Investigative ophthalmology & visual science · 2025Article
- Diabetes Advances Cardiomyocyte Senescence Through Interfering Rnd3 Expression and Function.Aging cell · 2025Article
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Article
- Cyclic Adenosine Monophosphate Signaling in Chronic Kidney Disease: Molecular Targets and Therapeutic Potentials.International journal of molecular sciences · 2024Review
- Biomarkers of Arginine Methylation in Diabetic Nephropathy: Novel Insights from Bioinformatics Analysis.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Article
- Kidney tea [Frontiers in pharmacology · 2024Article
- Relationship between Macrophages and Tissue Microenvironments in Diabetic Kidneys.Biomedicines · 2023Review
- Epsin1-mediated exosomal sorting of Dll4 modulates the tubular-macrophage crosstalk in diabetic nephropathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Identification of transcription factors related to diabetic tubulointerstitial injury.Journal of translational medicine · 2023Article
- GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy.Frontiers in immunology · 2023Article
- Histone H3K27 methyltransferase EZH2 regulates apoptotic and inflammatory responses in sepsis-induced AKI.Theranostics · 2023Article
- Review
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12 authors at 2 institutions in 1 country.
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Abstract
Tubulointerstitial inflammation plays an important role in the progression of diabetic nephropathy (DN), and tubular epithelial cells (TECs) are crucial promoters of the inflammatory cascade. Exchange protein activated by cAMP (Epac) has been shown to suppress the angiotensin II (Ang-II)-induced release of inflammatory cytokines in tubular cells. However, the role of Epac in TEC-mediated tubulointerstitial inflammation in DN remains unknown. We found that administering the Epac agonist 8-pCPT-2'-O-Me-cAMP (8-O-cAMP) to db/db mice inhibited tubulointerstitial inflammation characterized by macrophage infiltration and increased inflammatory cytokine release and consequently alleviated tubulointerstitial fibrosis in the kidney. Furthermore, 8-O-cAMP administration restored CCAAT/enhancer binding protein β (C/EBP-β) expression and further upregulated the expression of Suppressor of cytokine signaling 3 (SOCS3), while inhibiting p-STAT3, MCP-1, IL-6, and TNF-α expression in the kidney cortex in db/db mice. And in vitro study showed that macrophage migration and MCP-1 expression induced by high glucose (HG, 30 mM) were notably reduced by 8-O-cAMP in human renal proximal tubule epithelial (HK-2) cells. In addition, 8-O-cAMP treatment restored C/EBP-β expression in HK-2 cells and promoted C/EBP-β translocation to the nucleus, where it transcriptionally upregulated SOCS3 expression, subsequently inhibiting STAT3 phosphorylation. Under HG conditions, siRNA-mediated knockdown of C/EBP-β or SOCS3 in HK-2 cells partially blocked the inhibitory effect of Epac activation on the release of MCP-1. In contrast, SOCS3 overexpression inhibited HG-induced activation of STAT3 and MCP-1 expression in HK-2 cells. These findings indicate that Epac activation via 8-O-cAMP ameliorates tubulointerstitial inflammation in DN through the C/EBP-β/SOCS3/STAT3 pathway.
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