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: Yi Zhang, Wenju Lu, Kai Yang, Lei Xu, Ning Lai, Lichun Tian, Qian Jiang, Xin Duan, Minsheng Chen, Jian Wang
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 304 Issue 9 Pg. C833-43 (May 01 2013) ISSN: 1522-1563 [Electronic] United States
• PMID: 23447035 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bmp2 protein, rat
• Bmp4 protein, rat
• Bone Morphogenetic Protein 2
• Bone Morphogenetic Protein 4
• RNA, Small Interfering
• TRPC Cation Channels
• Calcium

Topics

• Animals
• Bone Morphogenetic Protein 2 (genetics, metabolism, physiology)
• Bone Morphogenetic Protein 4 (genetics, metabolism)
• Calcium (metabolism)
• Calcium Signaling
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Gene Expression
• Gene Expression Regulation
• Gene Knockdown Techniques
• Male
• Myocytes, Smooth Muscle (metabolism, physiology)
• Pulmonary Artery (cytology)
• RNA, Small Interfering (genetics)
• Rats
• Rats, Wistar
• TRPC Cation Channels (genetics, metabolism)