BMP4 Increases the Expression of TRPC and Basal Ca2 i via the p38MAPK and ERK1-2 Pathways Independent of BMPRII in PASMCsReportar como inadecuado




BMP4 Increases the Expression of TRPC and Basal Ca2 i via the p38MAPK and ERK1-2 Pathways Independent of BMPRII in PASMCs - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Yi Zhang , Yingfeng Wang , Kai Yang , Lichun Tian, Xin Fu, Yan Wang, Yueqian Sun, Qian Jiang, Wenju Lu , Jian Wang

Fuente: http://plos.srce.hr/



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