IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression
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 angioge...
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Elsevier
2025-07-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224003564 |
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| author | Jun-Hui Song Byungdoo Hwang Sung Lyea Park Hoon Kim Soontag Jung Changsun Choi Hwan Myung Lee Seok-Joong Yun Yung Hyun Choi Eun-Jong Cha Cam Patterson Wun-Jae Kim Sung-Kwon Moon |
| author_facet | Jun-Hui Song Byungdoo Hwang Sung Lyea Park Hoon Kim Soontag Jung Changsun Choi Hwan Myung Lee Seok-Joong Yun Yung Hyun Choi Eun-Jong Cha Cam Patterson Wun-Jae Kim Sung-Kwon Moon |
| author_sort | Jun-Hui Song |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-619aa9c6b2584ced809b6fca3912cbc3 |
| institution | OA Journals |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| series | Journal of Advanced Research |
| spelling | doaj-art-619aa9c6b2584ced809b6fca3912cbc32025-08-20T02:10:35ZengElsevierJournal of Advanced Research2090-12322025-07-017324726310.1016/j.jare.2024.08.013IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expressionJun-Hui Song0Byungdoo Hwang1Sung Lyea Park2Hoon Kim3Soontag Jung4Changsun Choi5Hwan Myung Lee6Seok-Joong Yun7Yung Hyun Choi8Eun-Jong Cha9Cam Patterson10Wun-Jae Kim11Sung-Kwon Moon12Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, KoreaDepartment of Food and Nutrition, Chung-Ang University, Anseong 456-756, KoreaDepartment of Food and Nutrition, Chung-Ang University, Anseong 456-756, KoreaDepartment of Food and Nutrition, Chung-Ang University, Anseong 456-756, KoreaDepartment of Food and Nutrition, Chung-Ang University, Anseong 456-756, KoreaDepartment of Food and Nutrition, Chung-Ang University, Anseong 456-756, KoreaDepartment of Cosmetic Science, Hoseo University, Asan-si 31499, Republic of KoreaPersonalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, South KoreaDepartment of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, South KoreaDepartment of Biomedical Engineering, Chungbuk National University, Cheongju 361-763, KoreaUniversity of Arkansas for Medical Sciences, Little Rock, AR, USAPersonalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea; Institute of Urotech, Cheongju, Chungcheongbuk-do 361-763, KoreaDepartment of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea; Corresponding author at: Department of Food and Nutrition, Chung-Ang University, Anseong 456-756, Republic of Korea.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.http://www.sciencedirect.com/science/article/pii/S2090123224003564IL-28AIL-10RβAngiogenesisHSP70-1 |
| spellingShingle | Jun-Hui Song Byungdoo Hwang Sung Lyea Park Hoon Kim Soontag Jung Changsun Choi Hwan Myung Lee Seok-Joong Yun Yung Hyun Choi Eun-Jong Cha Cam Patterson Wun-Jae Kim Sung-Kwon Moon IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression Journal of Advanced Research IL-28A IL-10Rβ Angiogenesis HSP70-1 |
| title | IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression |
| title_full | IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression |
| title_fullStr | IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression |
| title_full_unstemmed | IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression |
| title_short | IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression |
| title_sort | il 28a il 10rβ axis promotes angiogenesis via enos akt signaling and ap 1 nf κb mmp 2 network by regulating hsp70 1 expression |
| topic | IL-28A IL-10Rβ Angiogenesis HSP70-1 |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224003564 |
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