BMP4 increases the expression of TRPC and basal [Ca2+]i via the p38MAPK and ERK1/2 pathways independent of BMPRII in PASMCs
Multiple abnormalities of bone morphogenetic protein (BMPs) signaling are implicated in the process of pulmonary arterial hypertension (PAH). BMP4 plays an important role during the process of pulmonary arterial remodeling and mutant of the principle BMP4 receptor, BMP receptors II (BMPRII), is found to associate with the development of PAH. However, the likely mechanism defining the contribution of BMPRII to BMP4 mediated signaling in pulmonary arterial smooth muscle cells (PASMCs) remains comprehensively unclear. We previously found that enhanced store operated calcium entry (SOCE) and basal intracellular calcium concentration [Ca2+]i were induced by BMP4 via upregulation of TRPC1, 4 and 6 expression in PASMCs, and that BMP4 modulated TRPC channel expression through activating p38MAPK and ERK1/2 signaling pathways. In this study, BMPRII siRNA was used to knockdown BMPRII expression to investigate whether BMP4 upregulates the expression of TRPC and activating Smad1/5/8, ERK1/2 and p38MAPK pathway via BMPRII in distal PASMCs. Our results showed that knockdown of BMPRII: 1) attenuated BMP4 induced activation of P-Smad1/5/8, without altering BMP4 induced P-p38MAPK and P-ERK1/2 activation in PASMCs; 2) did not attenuate the BMP4-induced TRPC1, 4 and 6 expression; 3) did not affect BMP4-enhanced SOCE and basal [Ca2+]i. Thus, we concluded that BMP4 activated Smad1/5/8 pathway is BMPRII-dependent, while the BMP4 - ERK/p-P38 - TRPC - SOCE signaling axis are likely mediated through other receptor rather than BMPRII.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
PloS one - 9(2014), 12 vom: 28., Seite e112695 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.07.2015 Date Revised 22.03.2024 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0112695 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM24415662X |
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| 100 | 1 | |a Zhang, Yi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a BMP4 increases the expression of TRPC and basal [Ca2+]i via the p38MAPK and ERK1/2 pathways independent of BMPRII in PASMCs |
| 264 | 1 | |c 2014 | |
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| 500 | |a Date Completed 30.07.2015 | ||
| 500 | |a Date Revised 22.03.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Multiple abnormalities of bone morphogenetic protein (BMPs) signaling are implicated in the process of pulmonary arterial hypertension (PAH). BMP4 plays an important role during the process of pulmonary arterial remodeling and mutant of the principle BMP4 receptor, BMP receptors II (BMPRII), is found to associate with the development of PAH. However, the likely mechanism defining the contribution of BMPRII to BMP4 mediated signaling in pulmonary arterial smooth muscle cells (PASMCs) remains comprehensively unclear. We previously found that enhanced store operated calcium entry (SOCE) and basal intracellular calcium concentration [Ca2+]i were induced by BMP4 via upregulation of TRPC1, 4 and 6 expression in PASMCs, and that BMP4 modulated TRPC channel expression through activating p38MAPK and ERK1/2 signaling pathways. In this study, BMPRII siRNA was used to knockdown BMPRII expression to investigate whether BMP4 upregulates the expression of TRPC and activating Smad1/5/8, ERK1/2 and p38MAPK pathway via BMPRII in distal PASMCs. Our results showed that knockdown of BMPRII: 1) attenuated BMP4 induced activation of P-Smad1/5/8, without altering BMP4 induced P-p38MAPK and P-ERK1/2 activation in PASMCs; 2) did not attenuate the BMP4-induced TRPC1, 4 and 6 expression; 3) did not affect BMP4-enhanced SOCE and basal [Ca2+]i. Thus, we concluded that BMP4 activated Smad1/5/8 pathway is BMPRII-dependent, while the BMP4 - ERK/p-P38 - TRPC - SOCE signaling axis are likely mediated through other receptor rather than BMPRII | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Apoptosis Regulatory Proteins |2 NLM | |
| 650 | 7 | |a BMP4 protein, human |2 NLM | |
| 650 | 7 | |a Bone Morphogenetic Protein 4 |2 NLM | |
| 650 | 7 | |a Carrier Proteins |2 NLM | |
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| 650 | 7 | |a Mitochondrial Proteins |2 NLM | |
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| 650 | 7 | |a TRPC Cation Channels |2 NLM | |
| 650 | 7 | |a p38 Mitogen-Activated Protein Kinases |2 NLM | |
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| 650 | 7 | |a Bone Morphogenetic Protein Receptors, Type II |2 NLM | |
| 650 | 7 | |a EC 2.7.11.30 |2 NLM | |
| 700 | 1 | |a Wang, Yingfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Lichun |e verfasserin |4 aut | |
| 700 | 1 | |a Fu, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yueqian |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Wenju |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jian |e verfasserin |4 aut | |
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