Shuai Zhang1, Lihui Zou2, Ting Yang1, Yuanhua Yang1, Zhenguo Zhai1, Fei Xiao2, Chen Wang3. 1. Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing, PR China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing, PR China. 2. Institute of Geriatrics, Beijing Hospital, 1 Dahua Rd, Beijing, PR China; National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing, PR China. 3. Beijing Institute of Respiratory Medicine, Beijing Chao-yang Hospital, Capital Medical University, 8 Gongti South Rd, Beijing, PR China; Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, 8 Gongti South Rd, Beijing, PR China; National Clinical Research Center for Respiratory Diseases, 1 Dahua Rd, Beijing, PR China. Electronic address: chenwangcjfh@163.com.
Abstract
BACKGROUND: Different types of pulmonary hypertension (PH) share the same process of pulmonary vascular remodeling, the molecular mechanism of which is not entirely clarified by far. The abnormal biological behaviors of pulmonary arterial smooth muscle cells (PASMCs) play an important role in this process. OBJECTIVES: We investigated the regulation of plasminogen activator inhibitor-2 (PAI-2) by the sGC activator, and explored the effect of PAI-2 on PASMCs proliferation, apoptosis and migration. METHODS: After the transfection with PAI-2 overexpression vector and specific siRNAs or treatment with BAY 41-2272 (an activator of sGC), the mRNA and protein levels of PAI-2 in cultured human PASMCs were detected, and the proliferation, apoptosis and migration of PASMCs were investigated. RESULTS: BAY 41-2272 up regulated the endogenous PAI-2 in PASMCs, on the mRNA and protein level. In PAI-2 overexpression group, the proliferation and migration of PASMCs were inhibited significantly, and the apoptosis of PASMCs was increased. In contrast, PAI-2 knockdown with siRNA increased PASMCs proliferation and migration, inhibited the apoptosis. CONCLUSIONS: PAI-2 overexpression inhibits the proliferation and migration and promotes the apoptosis of human PASMCs. Therefore, sGC activator might alleviate or reverse vascular remodeling in PH through the up-regulation of PAI-2.
BACKGROUND: Different types of pulmonary hypertension (PH) share the same process of pulmonary vascular remodeling, the molecular mechanism of which is not entirely clarified by far. The abnormal biological behaviors of pulmonary arterial smooth muscle cells (PASMCs) play an important role in this process. OBJECTIVES: We investigated the regulation of plasminogen activator inhibitor-2 (PAI-2) by the sGC activator, and explored the effect of PAI-2 on PASMCs proliferation, apoptosis and migration. METHODS: After the transfection with PAI-2 overexpression vector and specific siRNAs or treatment with BAY 41-2272 (an activator of sGC), the mRNA and protein levels of PAI-2 in cultured humanPASMCs were detected, and the proliferation, apoptosis and migration of PASMCs were investigated. RESULTS:BAY 41-2272 up regulated the endogenous PAI-2 in PASMCs, on the mRNA and protein level. In PAI-2 overexpression group, the proliferation and migration of PASMCs were inhibited significantly, and the apoptosis of PASMCs was increased. In contrast, PAI-2 knockdown with siRNA increased PASMCs proliferation and migration, inhibited the apoptosis. CONCLUSIONS:PAI-2 overexpression inhibits the proliferation and migration and promotes the apoptosis of humanPASMCs. Therefore, sGC activator might alleviate or reverse vascular remodeling in PH through the up-regulation of PAI-2.
Authors: Wayne A Schroder; Thiago D Hirata; Thuy T Le; Joy Gardner; Glen M Boyle; Jonathan Ellis; Eri Nakayama; Dilan Pathirana; Helder I Nakaya; Andreas Suhrbier Journal: Sci Rep Date: 2019-08-27 Impact factor: 4.379