Cerebellin-2 promotes endothelial-mesenchymal transition in hypoxic pulmonary hypertension rats by activating NF-κB/HIF-1α/Twist1 pathway.

Autor: Wang EL; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China., Zhang JJ; Department of Obstetrics, Xiangya Hospital, Central South University, Changsha 410008, China., Luo FM; Department of Pharmacy, Hunan Children's Hospital, Changsha 410007, China., Fu MY; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China., Li D; Phase I Clinical Trial Center, Xiangya Hospital, Central South University, Changsha 410008, China., Peng J; Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China., Liu B; Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China; Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China. Electronic address: liubin@csu.edu.cn.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Sep 01; Vol. 328, pp. 121879. Date of Electronic Publication: 2023 Jun 22.
DOI: 10.1016/j.lfs.2023.121879
Abstrakt: Aims: Endothelial-mesenchymal transition (EndMT) is one of the critical factors leading to vascular remodeling in pulmonary hypertension (PH). Recent studies found that the expression of Cerebellin-2 (CBLN2) is significantly increased in the lung tissue of patients with PH, suggesting that CBLN2 may be closely related to the development of PH. This study aims to investigate the role and potential mechanism of CBLN2 in the hypoxia-induced EndMT of PH rats.
Material and Methods: Hypoxia-induced PH rat model or EndMT cell model was constructed to investigate the role of CBLN2 in the process of endothelial mesenchymal transition during PH. The effects of CBLN2 siRNA, KC7F2 (HIF-1α inhibitor), and PDTC (NF-κB inhibitor) on hypoxia-induced EndMT were observed to evaluate the potential mechanism of CBLN2 in promoting EndMT.
Key Findings: The right ventricular systolic pressure and pulmonary vascular remodeling index in hypoxia-treated rats were significantly increased. The transformation of endothelial cells (marked by CD31) to mesenchymal cells (marked by α-SMA) can be observed in the pulmonary vessels of PH rats, and the expression of CBLN2 in the intima was also significantly up-regulated. In the hypoxia-induced HPAECs, endothelial cell markers such as VE-cadherin and CD31 expression were significantly down-regulated, while mesenchymal-like cell markers such as α-SMA and vimentin were increased considerably, along with the increased expressions of CBLN2, p-p65, HIF-1α, and Twist1; CBLN2 siRNA, PDTC, and KC7F2 could inhibit those phenomena.
Significance: CBLN2 can promote EndMT by activating NF-κB/HIF-1α/Twist1 pathway. Therefore, CBLN2 may be a new therapeutic target for PH.
Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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