ArticleJournal of advanced research2025
IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression.
Article in Journal of advanced research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Inhibition of Fibroblast Activation Protein-α Ameliorates Intervertebral Disc Degeneration via Reduced Vascular Invasion in Cartilage Endplate.Cell proliferation · 2026Article
- Dermal mesenchymal stem cells promote angiogenesis in HMEC-1 via activation of the angiopoietin 1/Tie2 pathway in psoriasis.Frontiers in cell and developmental biology · 2026Article
- Recent insights into HSP70: proteostasis and beyond.Frontiers in molecular biosciences · 2026Review
- The cardiovascular-immune axis: crosstalk and therapy in atherosclerosis, myocarditis and vasculitis.Frontiers in immunology · 2026Review
- Review
- L-arginine: A promising metabolite in enhancing the protective effects of adipose-derived stem cells against ischemic pathologies.World journal of stem cells · 2025Article
- Identification of tRF-29-79MP9P9NH525 as a biomarker and tumor suppressor of gastric cancer via regulating KIF14/AKT pathway.Cell death discovery · 2025Article
- MAPK/ERK Signaling in Tumorigenesis: mechanisms of growth, invasion, and angiogenesis.EXCLI journal · 2025Review
- Article
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Authors and funding
13 authors.
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Abstract
introductionAngiogenesis plays a significant role in the development of tumor progression and inflammatory diseases. The role of IL-28A in angiogenesis and its precise regulatory mechanisms remain rarely elucidated.
objectivesWe report the novel regulatory role of IL-28A in physiological angiogenesis. The study aimed to elucidate the regulatory mechanisms involved in IL-28A-mediated angiogenesis and identify key genes associated with IL-28A-induced angiogenic responses.
methodsTo know the effect of IL-28A on angiogenesis, HUVECs were applied to perform proliferation, migration, invasion, tube formation, immunoblot, and EMSA. Gene expression changes in HUVECs following IL-28A treatment were analyzed by NGS. The functional role of HSP70-1 and IL-10Rβ in IL-28A-induced angiogenic responses was evaluated using PCR and siRNA knockdown. Animal studies were conducted by aortic ring ex vivo assays, Matrigel plug in vivo assays, and immunochemistry using HSP70-1 knockout and transgenic mice models. The efficacy of IL-28A in angiogenesis was confirmed in a hind-limb ischemia model.
resultsAutocrine/paracrine actions in HUVECs regulated IL-28A protein expression. Exogenous IL-28A increased the proliferation of HUVECs via eNOS/AKT and ERK1/2 signaling. IL-28A treatment promoted migration, invasion, and capillary tube formation of HUVECs through induction of the AP-1/NF-κB/MMP-2 network, which was associated with eNOS/AKT and ERK1/2 signaling. The efficacy of IL-28A-induced angiogenic potential was confirmed by aortic ring and Matrigel plug assay. HSP70-1 was identified as an IL-28A-mediated angiogenic effector gene using bioinformatics. Knockdown of HSP70-1 abolished angiogenic responses and eNOS/AKT signaling in IL-28A-treated HUVECs. IL-28A-induced microvessel sprouting formation was testified in HSP70-1-deficient and HSP70-1 transgenic mice. Flow recovery in hind-limb ischemia mice was accelerated by IL-28A injection. Finally, ablation of the IL-10Rβ gene impeded the angiogenic responses and eNOS/AKT signaling stimulated by IL-28A in HUVECs.
conclusionHSP70-1 drives the progression of angiogenesis by the IL-28A/IL-10Rβ axis via eNOS/AKT signaling and the AP-1/NF-κB/MMP-2 network.
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