APELIN-13 AMELIORATES LPS-INDUCED ENDOTHELIAL-TO-MESENCHYMAL TRANSITION AND POST-ACUTE LUNG INJURY PULMONARY FIBROSIS BY SUPPRESSING TRANSFORMING GROWTH FACTOR-B1 SIGNALING

作者全名："Liu, Huang; Shi, Qingqiang; Tang, Ling; Wang, Hanghang; Wang, Daoxin"

作者地址："[Liu, Huang; Shi, Qingqiang; Tang, Ling; Wang, Hanghang; Wang, Daoxin] Chongqing Med Univ, Affiliated Hosp 2, Dept Resp Med, Chongqing, Peoples R China; [Wang, Daoxin] 74 Linjiang Rd, Chongqing 400010, Peoples R China"

通信作者："Wang, DX (通讯作者)，74 Linjiang Rd, Chongqing 400010, Peoples R China."

来源：SHOCK

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000922943100015

JCR分区：Q1

影响因子：2.7

年份：2023

卷号：59

期号：1

开始页：108

结束页：117

文献类型：Article

关键词：Acute lung injury; apelin-13; endothelial-to-mesenchymal transition; pulmonary fibrosis; sepsis; TGF-beta 1

摘要："The pathophysiology of acute respiratory distress syndrome (ARDS) involves cytokine storms, alveolar-capillary barrier destruction, and fibrotic progression. Pulmonary interstitial fibrosis is an important factor affecting the prognosis of ARDS patients. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the development of fibrotic diseases, and the occurrence of EndMT has been observed in experimental models of LPS-induced acute lung injury (ALI). Apelin is an endogenous active polypeptide that plays an important role in maintaining endothelial cell homeostasis and inhibiting fibrotic progression in various diseases. However, whether apelin attenuates EndMT in ALI and post-ALI pulmonary fibrosis remains unclear. We analyzed the serum levels of apelin-13 in patients with sepsis-associated ARDS to examine its possible clinical value. A murine model of LPS-induced pulmonary fibrosis and an LPS-challenged endothelial cell injury model were used to analyze the protective effect and underlying mechanism of apelin-13. Mice were treated with apelin-13 by i.p. injection, and human pulmonary microvascular endothelial cells were incubated with apelin-13 in vitro. We found that the circulating apelin-13 levels were significantly elevated in sepsis-associated ARDS patients compared with healthy controls. Our study also confirmed that LPS induced EndMT progression and pulmonary fibrosis, which were characterized by decreased CD31 expression and increased alpha-smooth muscle actin expression and collagen deposition. LPS also stimulated the production of transforming growth factor beta 1 and activated the Smad signaling pathway. However, apelin-13 treatment significantly attenuated these changes. Our findings suggest that apelin-13 may be a novel biomarker in patients with sepsis-associated ARDS. These results demonstrate that apelin-13 ameliorates LPS-induced EndMT and post-ALI pulmonary fibrosis by suppressing transforming growth factor beta 1 signaling."

基金机构："Outstanding Talent Program of Chongqing, China [CQYC20200321]; Natural Science Foundation of Chongqing, China [cstc2019jcyj-zdxmX0031]"

基金资助正文："This study was supported by the Outstanding Talent Program of Chongqing, China (grant CQYC20200321) and Natural Science Foundation of Chongqing, China (grant cstc2019jcyj-zdxmX0031)."