Uric acid induced the phenotype transition of vascular endothelial cells via induction of oxidative stress and glycocalyx shedding
- 주제(키워드) EndoMT , reactive oxygen species , hyperuricemia , syndecan-1
- 주제(기타) Biochemistry & Molecular Biology; Biology; Cell Biology
- 설명문(일반) [Ko, Jiyeon; Kang, Hyun-Jung; Kim, Dal-Ah; Ryu, Eun-Sun; Lee, Shina; Ryu, Jung-Hwa; Kang, Duk-Hee] Ewha Womans Univ, Coll Med, Ewha Med Res Ctr, Div Nephrol,Dept Internal Med, Seoul, South Korea; [Kim, Mi-Jin] CHA Univ, Dept Biotechnol, Seongnam, South Korea; [Roncal, Carlos; Johnson, Richard J.] Univ Colorado, Div Renal Dis & Hypertens, Anschutz Med Campus, Aurora, CO USA
- 등재 SCIE, SCOPUS
- OA유형 Bronze
- 발행기관 FEDERATION AMER SOC EXP BIOL
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000166124
- 본문언어 영어
- Published As http://dx.doi.org/10.1096/fj.201901148R
- PubMed https://pubmed.ncbi.nlm.nih.gov/31553887
초록/요약
Recent data suggested a causative role of uric acid (UA) in the development of renal disease, in which endothelial dysfunction is regarded as the key mechanism. Endothelial-to-mesenchymal transition (EndoMT) and shedding of the glycocalyx are early changes of endothelial dysfunction. We investigated whether UA induced EndoMT in HUVECs and an animal model of hyperuricemia fed with 2% oxonic acid for 4 wk. UA induced EndoMT in HUVECs with a generation of reactive oxygen species via the activation of membranous NADPH oxidase (from 15 min) and mitochondria (from 6 h) along with glycocalyx shedding (from 6 h), which were blocked by probenecid. GM6001, an inhibitor of matrix metalloproteinase, alleviated UA-induced glycocalyx shedding and EndoMT. Antioxidants including N-acetyl cysteine, apocynin, and mitotempo ameliorated EndoMT; however, they did not change glycocalyx shedding in HUVECs. In the kidney of hyperuricemic rats, endothelial staining in peritubular capillaries (PTCs) was substantially decreased with a de novo expression of alpha-smooth muscle actin in PTCs. Plasma level of syndecan-1 was increased in hyperuricemic rats, which was ameliorated by allopurinol. UA caused a phenotypic transition of endothelial cells via induction of oxidative stress with glycocalyx shedding, which could be one of the mechanisms of UA-induced endothelial dysfunction and kidney disease.
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