Chemerin Regulates the Proliferation and Migration of Pulmonary Arterial Smooth Muscle Cells via the ERK1/2 Signaling Pathway

Linqian Peng; Yunwei Chen; Yan Li; Panpan Feng; Yan Zheng; Yongjie Dong; Yunjing Yang; Ruiyu Wang; Ailing Li; Jianghong Yan; Feifei Shang; Ping Tang; Dewei Chen; Yuqi Gao; Wei Huang

doi:10.3389/fphar.2022.767705

Chemerin Regulates the Proliferation and Migration of Pulmonary Arterial Smooth Muscle Cells via the ERK1/2 Signaling Pathway

Front Pharmacol. 2022 Mar 18:13:767705. doi: 10.3389/fphar.2022.767705. eCollection 2022.

Authors

Linqian Peng^{1

2}, Yunwei Chen^{1

2}, Yan Li^{1

2}, Panpan Feng¹, Yan Zheng^{1

2}, Yongjie Dong^{1

2}, Yunjing Yang¹, Ruiyu Wang^{1

2}, Ailing Li¹, Jianghong Yan², Feifei Shang², Ping Tang¹, Dewei Chen³, Yuqi Gao³, Wei Huang¹

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² Institute of Life Science, Chongqing Medical University, Chongqing, China.
³ Institute of Medicine and Equipment for High Altitude Region, College of High Altitude Military Medicine, Army Medical University, Chongqing, China.

Abstract

Pulmonary arterial hypertension (PAH) is an incurable disease with high mortality. Chemerin has been found to be associated with pulmonary hypertension (PH). However, the specific role of chemerin in mediating PH development remains unclear. This study aimed to elucidate the regulatory effects and the underlying mechanism of chemerin on PH and to investigate the expression levels of chemerin protein in plasma in PAH patients. In vivo, two animal models of PH were established in rats by monocrotaline (MCT) injection and hypoxia. We found that the expression levels of chemerin and its receptor, chemokine-like receptor 1 (CMKLR1), were significantly upregulated in the lungs of PH rats. Primary cultured pulmonary arterial smooth muscle cells [(PASMCs) (isolated from pulmonary arteries of normal healthy rats)] were exposed to hypoxia or treated with recombinant human chemerin, we found that CMKLR1 expression was upregulated in PASMCs in response to hypoxia or chemerin stimulation, whereas the exogenous chemerin significantly promoted the migration and proliferation of PASMCs. Notably, the regulatory effects of chemerin on PASMCs were blunted by PD98059 (a selective ERK1/2 inhibitor). Using enzyme linked immunosorbent assay (ELISA), we found that the protein level of chemerin was also markedly increased in plasma from idiopathic pulmonary arterial hypertension (IPAH) patients compared to that from healthy controls. Moreover, the diagnostic value of chemerin expression in IPAH patients was determined through receiver operating characteristic (ROC) curve analysis and the result revealed that area under ROC curve (AUC) for plasma chemerin was 0.949. Taken together, these results suggest that chemerin exacerbates PH progression by promoting the proliferation and migration of PASMCs via the ERK1/2 signaling pathway, and chemerin is associated with pulmonary hypertension.

Keywords: ERK1/2; chemerin; chemokine-like receptor 1; pulmonary arterial hypertension; pulmonary arterial smooth muscle cells.