문성권 (중앙대학교)

한빛사논문

조회116

문성권Sung-Kwon Moon

중앙대학교

J. Adv. Res., Aug 08 2024, S2090-1232(24)00356-4 | https://doi.org/10.1016/j.jare.2024.08.013 IL-28A/IL-10Rβ axis promotes angiogenesis via eNOS/AKT signaling and AP-1/NF-κB/MMP-2 network by regulating HSP70-1 expression

Jun-Hui Song ^a,1, Byungdoo Hwang ^a,1, Sung Lyea Park ^a, Hoon Kim ^a, Soontag Jung ^a, Changsun Choi ^a, Hwan Myung Lee ^b, Seok-Joong Yun ^c, Yung Hyun Choi ^d, Eun-Jong Cha ^e, Cam Patterson ^f, Wun-Jae Kim^c,g, Sung-Kwon Moon ^a

^aDepartment of Food and Nutrition, Chung-Ang University, Anseong 456-756, Korea

^bDepartment of Cosmetic Science, Hoseo University, Asan-si 31499, Republic of Korea

^cPersonalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea

^dDepartment of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, South Korea

^eDepartment of Biomedical Engineering, Chungbuk National University, Cheongju 361-763, Korea

^fUniversity of Arkansas for Medical Sciences, Little Rock, AR, USA

^gInstitute of Urotech, Cheongju, Chungcheongbuk-do 361-763, Korea

¹These authors contributed equally to this work.

Corresponding author: Sung-Kwon Moon

Abstract

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.

논문정보

형식Research article
게재일2024년 08월 (BRIC 등록일 2024-08-12)
연구진국내(교신)+국외 연구진
분야 생명과학 > 세포생물학

댓글 작성 로그인

CV 열람하기

연락처 보기