한빛사논문
- 조회557
Tae Kyeong Kim1,10, Sejin Jeon1,8,10, Seonjun Park2, Seong-Keun Sonn1, Seungwoon Seo1, Joowon Suh1, Jing Jin1, Hyae Yon Kweon1, Sinai Kim1, Shin Hye Moon1, Okhee Kweon1, Bon-Hyeock Koo3,9, Nayoung Kim4,5, Hae-Ock Lee4,5, Young-Myeong Kim6, Young-Joon Kim7, Sung Ho Park2 & Goo Taeg Oh1
1Heart-Immune-Brain Network Research Center, Department of Life Sciences, Ewha Womans University, Seoul, Republic of Korea.
2Department of Biological Sciences, Ulsan National Institute of Science & Technology (UNIST), Ulsan, Republic of Korea.
3Department of Biological Sciences, Kangwon National University, Kangwondae-gil 1, Chuncheon, Republic of Korea.
4Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
5Department of Biomedicine and Health Sciences, Graduate School, The Catholic University of Korea, Seoul, Republic of Korea.
6Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Kangwondae-gil 1, Chuncheon 24341, Republic of Korea.
7Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.
8Present address: Department of Biological Sciences and Biotechnology Major in Bio-Vaccine Engineering, Andong National University, Andong, Gyeongsangbuk-do, Republic of Korea.
9Present address: McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6081, USA.
10These authors contributed equally: Tae Kyeong Kim, Sejin Jeon
Corresponding author : Correspondence to Goo Taeg Oh
Abstract
Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection. In this study, we demonstrate a regulatory role for endothelial expression of 2'-5' oligoadenylate synthetase-like 1 (OASL1) in maintaining eNOS mRNA stability during athero-prone conditions and consider its clinical implications. A lack of endothelial Oasl1 accelerated plaque progression, which was preceded by endothelial dysfunction, elevated vascular inflammation, and decreased NO bioavailability following impaired eNOS expression. Mechanistically, knockdown of PI3K/Akt signaling-dependent OASL expression increased Erk1/2 and NF-κB activation and decreased NOS3 (gene name for eNOS) mRNA expression through upregulation of the negative regulatory, miR-584, whereas a miR-584 inhibitor rescued the effects of OASL knockdown. These results suggest that OASL1/OASL regulates endothelial biology by protecting NOS3 mRNA and targeting miR-584 represents a rational therapeutic strategy for eNOS maintenance in vascular disease.
논문정보
- Research article
- 2022년 11월 (BRIC 등록일 2023-01-04)
- 국내(교신)+국외 연구진
- 생명과학 > 유전학
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