Hypoxia decrease expression of cartilage oligomeric matrix protein to promote phenotype switching of pulmonary arterial smooth muscle cells.

Abstract

Extracellular matrix proteins play important roles in the development of pulmonary hypertension(pH). However, the role of Cartilage oligomeric matrix protein (COMP) in the development of hypoxia-induced pH is largely unknown. We tested the hypothesis that COMP deficiency induced by hypoxia leads to the phenotype switching of pulmonary arterial smooth muscle cells (PASMCs). The expression of COMP decreased in a chronic hypoxia rat pH model (P<0.05) and in PASMCs under hypoxia (3%O2) (P<0.05). The expressions of differentiated marker proteins reduced in the pulmonary arteries from 5 month old COMP-/- mice and in PASMCs under hypoxia or with the siRNA of COMP treatment under normoxia, but increased in PASMCs with adenovirus-increased COMP under hypoxia. The absorbance of cell counting kit-8 at 450nm and the expressions of proliferating cell nuclear antigen (PCNA) and osteopontin increased in PASMCs with the siRNA of COMP under normoxia (P<0.05). PCNA and osteopontin decreased in PASMCs with adenovirus-increased COMP under hypoxia (P<0.05). Additionally, the expression of bone morphogenetic protein receptor 2 (BMPR2) was reduced in COMP-/- mice (P<0.01). Both mRNA and protein levels of bone morphogenetic protein 2 (BMP2) were lower in PASMCs with the siRNA of COMP (P<0.05). The protein level of BMP2 could be reversed by adenovirus-increased COMP under hypoxia (P<0.05). These data suggest that COMP could normally have a protective role against PASMC phenotype switching and maintain BMP2/BMPR2 signaling, and these protective actions could be lost as a result of hypoxia promoting a depletion of COMP.

• Authors: Hang Yu, Qingbo Jia, Xiaoqian Feng, Hongxia Chen, Liang Wang, Xiuqin Ni, Wei Kong
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 91 Issue Pt A Pg. 37-44 (10 2017) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 28860005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• Bmp2 protein, mouse
• Bone Morphogenetic Protein 2
• Cartilage Oligomeric Matrix Protein
• Bmpr2 protein, mouse
• Bone Morphogenetic Protein Receptors, Type II

Topics

• Animals
• Bone Morphogenetic Protein 2 (metabolism)
• Bone Morphogenetic Protein Receptors, Type II (metabolism)
• Cartilage Oligomeric Matrix Protein (genetics, metabolism)
• Cell Differentiation
• Cell Hypoxia
• Cell Proliferation
• Female
• Gene Expression Regulation
• Hemodynamics
• Lung (physiology)
• Male
• Mice
• Myocytes, Smooth Muscle (cytology)
• Phenotype
• Pulmonary Artery (cytology)
• Rats