title: Bone morphogenetic protein 2 decreases TRPC expression, store-operated Ca(2+) entry, and basal [Ca(2+)]i in rat distal pulmonary arterial smooth muscle cells.
abstract: Recent studies indicate that multiple bone morphogenetic protein (BMP) family ligands and receptors are involved in the development of pulmonary arterial hypertension, yet the underlying mechanisms are incompletely understood. Although BMP2 and BMP4 share high homology in amino acid sequence, they appear to exert divergent effects on chronic hypoxic pulmonary hypertension (CHPH). While BMP4 promotes vascular remodeling, BMP2 prevents CHPH. We previously demonstrated that BMP4 upregulates the expression of canonical transient receptor potential channel (TRPC) proteins and, thereby, enhances store-operated Ca(2+) entry (SOCE) and elevates intracellular Ca(2+) concentration ([Ca(2+)]i) in pulmonary arterial smooth muscle cells (PASMCs). In this study, we investigated the effects of BMP2 on these variables in rat distal PASMCs. We found that treatment with BMP2 (50 ng/ml, 60 h) inhibited TRPC1, TRPC4, and TRPC6 mRNA and protein expression. Moreover, BMP2 treatment led to reduced SOCE and decreased basal [Ca(2+)]i in PASMCs. These alterations were associated with decreased PASMC proliferation and migration. Conversely, knockdown of BMP2 with specific small interference RNA resulted in increased cellular levels of TRPC1, TRPC4, and TRPC6 mRNA and protein, enhanced SOCE, elevated basal [Ca(2+)]i, and increased proliferation and migration of PASMCs. Together, these results indicate that BMP2 participates in regulating Ca(2+) signaling in PASMCs by inhibiting TRPC1, TRPC4, and TRPC6 expression, thus leading to reduced SOCE and basal [Ca(2+)]i and inhibition of cell proliferation and migration.
authors: State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Disease, Guangzhou, China.
authors: Yi
authors: Y
authors: Zhang
authors: Wenju
authors: W
authors: Lu
authors: Kai
authors: K
authors: Yang
authors: Lei
authors: L
authors: Xu
authors: Ning
authors: N
authors: Lai
authors: Lichun
authors: L
authors: Tian
authors: Qian
authors: Q
authors: Jiang
authors: Xin
authors: X
authors: Duan
authors: Minsheng
authors: M
authors: Chen
authors: Jian
authors: J
authors: Wang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D015870:Gene Expression; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000502:physiology; D011651:Pulmonary Artery / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D050052:TRPC Cation Channels / Q000235:genetics* / Q000378:metabolism
chemical_list: C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D034741:RNA, Small Interfering; D050052:TRPC Cation Channels; D002118:Calcium
keywords: BMP2; calcium signaling; pulmonary arterial smooth muscle cells; transient receptor potential canonical