Ubiquitination of angiotensin-converting enzyme 2 contributes to the development of pulmonary arterial hypertension mediated by neural precursor cell-expressed developmentally down-regulated gene 4-Like.

Autor: Wang R; Graduate School, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, China.; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, Jiangsu, China., Wang R; Department of Orthopedics, Xuzhou Central Hospital, 199 Jiefang South Road, Quanshan District, Xuzhou, Jiangsu, China., Zhou S; Department of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, 321 Zhongshan Road, Drum Tower District, Nanjing, Jiangsu, China., Liu T; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, Jiangsu, China., Dang J; Graduate School, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, China.; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, Jiangsu, China., Chen Q; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, Jiangsu, China., Chen J; Graduate School, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, China., Wang Z; Graduate School, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing, Jiangsu, China. zhpsqxt@126.com.; Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, No.99 Huaihai West Road, Xuzhou, Jiangsu, China. zhpsqxt@126.com.
Jazyk: angličtina
Zdroj: Respiratory research [Respir Res] 2024 Aug 29; Vol. 25 (1), pp. 326. Date of Electronic Publication: 2024 Aug 29.
DOI: 10.1186/s12931-024-02953-5
Abstrakt: Objectives: In this study, we investigated whether neural precursor cell-expressed developmentally down-regulated gene 4-like (NEDD4L) is the E3 enzyme of angiotensin-converting enzyme 2 (ACE2) and whether NEDD4L degrades ACE2 via ubiquitination, leading to the progression of pulmonary arterial hypertension (PAH).
Methods: Bioinformatic analyses were used to explore the E3 ligase that ubiquitinates ACE2. Cultured pulmonary arterial smooth muscle cells (PASMCs) and specimens from patients with PAH were used to investigate the crosstalk between NEDD4L and ACE2 and its ubiquitination in the context of PAH.
Results: The inhibition of ubiquitination attenuated hypoxia-induced proliferation of PASMCs. The levels of NEDD4L were increased, and those of ACE2 were decreased in lung tissues from patients with PAH and in PASMCs. NEDD4L, the E3 ligase of ACE2, inhibited the expression of ACE2 in PASMCs, possibly through ubiquitination-mediated degradation. PAH was associated with upregulation of NEDD4L expression and downregulation of ACE2 expression.
Conclusions: NEDD4L, the E3 ubiquitination enzyme of ACE2, promotes the proliferation of PASMCs, ultimately leading to PAH.
(© 2024. The Author(s).)
Databáze: MEDLINE
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