Original Research ARTICLE
17β-estradiol promotes apoptosis in airway smooth muscle cells through CD38/SIRT1/p53 pathway
- 1Nanchang University, China
- 2First Affiliated Hospital of Nanchang University, China
17β-Estradiol (E2) is the major estrogen secreted by the premenopausal ovary and shows dual effects on cell apoptosis under pathological conditions. E2 was previously shown to increase CD38 mRNA and protein expression in myometrial smooth muscle, but its function and mechanism remain largely unknown. Here we investigated the role of E2 in hypoxia-induced apoptosis in mouse airway smooth muscle cells (ASMCs) and explored the underlying mechanisms. Results showed that E2 significantly increased CD38 expression at both mRNA and protein levels, accompanied with decreased SIRT1 levels in ASMCs. By using primary ASMCs from the wild type (WT) and the smooth muscle-specific CD38 knockout (CD38 KO) mice, we found that the down-regulation of SIRT1 induced by E2 was abolished in CD38 KO AMSCs. E2 promoted the acetylation of p53 in WT cells, and this effect was also diminished in the absence of CD38. In addition, E2 further activated CD38/SIRT1/p53 signal pathway and promoted cell apoptosis during hypoxia. However, these effects were reversed in CD38 KO ASMCs and by the specific SIRT1 activator Resveratrol. We also found that E2 enhanced CD38 expression through estrogen receptor.The data suggested that CD38 is a direct target for E2 which promotes hypoxia-induced AMSC apoptosis through SIRT1/p53 signal pathway.
Keywords: E2, CD38, SIRT1, hypoxia, Apoptosis
Received: 30 Jul 2018;
Accepted: 06 Dec 2018.
Edited by:Yang Yang, Northwest University, China
Reviewed by:Roman L. Bogorad, Puretech Health, Inc., United States
Sudan He, Soochow University, China
Tadashi Nakagawa, Tohoku University, Japan
Wen Zhou, Case Western Reserve University, United States
Copyright: © 2018 Liu, Guo, Huang, Deng, Qian and Xin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Dr. Yisong Qian, Nanchang University, Nanchang, China, firstname.lastname@example.org
Prof. Hong-Bo Xin, Nanchang University, Nanchang, China, email@example.com