IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression.

Autor:	Song JH; Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea., Hwang B; Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea., Lyea Park S; Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea., Kim H; Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea., Jung S; Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea., Choi C; Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea., Myung Lee H; Department of Cosmetic Science, Hoseo University, Asan-si 31499, Republic of Korea., Yun SJ; Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea., Hyun Choi Y; Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, South Korea., Cha EJ; Department of Biomedical Engineering, Chungbuk National University, Cheongju 361-763, Korea., Patterson C; University of Arkansas for Medical Sciences, Little Rock, AR, USA., Kim WJ; Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea; Institute of Urotech, Cheongju, Chungcheongbuk-do 361-763, Korea., Moon SK; Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea. Electronic address: sumoon66@cau.ac.kr.
Jazyk:	angličtina
Zdroj:	Journal of advanced research [J Adv Res] 2024 Aug 09. Date of Electronic Publication: 2024 Aug 09.
DOI:	10.1016/j.jare.2024.08.013
Abstrakt:	Introduction: Angiogenesis 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. Objectives: We 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. Methods: To 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. Results: Autocrine/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. Conclusion: HSP70-1 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. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2024. Production and hosting by Elsevier B.V.)
Databáze:	MEDLINE
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