These results suggest that BMP4 induced Smad1/5/ 8 pathway is activated via BMPRII. However, BMPRII was determined not involved in BMP4 induced ERK1/2 and p38MAPK pathway activation. It is consistent with our preliminary result which indicated that BMP4 modulate TRPC channel expression through p38MAPK and ERK1/2 pathways. Although Smad1/5/8 is generally considered as a key component of the canonical BMP signal transduction pathway, our data suggest that BMP4 induced TRPC1, 4 and 6 enhancement is dependent on p38MAPK and ERK1/2, but not Smad1/5/8. Recent studies demonstrated that abnormal expression of TRPC is an important factor in artery remodeling during PAH development. Proliferating PASMCs are found associated with increased TRPC1 expression. In contrast, reduction of TRPC1 expression attenuates the proliferation of PASMCs. Moreover, change in TRPC1 expression has been confirmed along with apoptosis. Next, our results AMN107 further showed that BMP4 could lead to enhancement of SOCE and basal i in the absence of BMPRII. The results are consistent with our above-mentioned findings, which indicate that BMPRII didn9t contribute to the regulation of Ca2+ signaling by modulating BMP4 induced TRPC channel expression. Given the fact that BMPRII is unrelated to BMP4 induced elevated SOCE and basal i, here came the hypothesis that other BMP receptors are potentially responsible for these subsequent outcomes of BMP4 treatment. Although people have obtained data suggesting that BMP4 mediate signaling through other candidates such as ALK2, BMPRIa, BMPRIb, ActRIIa and ActRIIb, the precise molecular mechanisms remain largely unknown. Many advances have confirmed that excision of BMPRII may drive BMP4 tend to combine with other type II receptors such as ActRII through utilizing coreceptor repulsive guidance molecule RGMa and result in the reduction of Smads pathway activation, without disrupting the activation of p38MAPK and ERK1/2 in PASMCs. Based on these previous evidence, a further study was then undertaken to identify the expression profile of all the six known BMP receptors ActRII2a, ActRII2b, ALK2, BMPRIa and BMPRIb. We found that ActRIIa and ActRIIb were selectively upregulated by BMP4 treatment. These results strongly suggest ActR2a and ActR2b mignt act as the potential candidates to charge for the excessive BMP4 induced downstream activation of p-ERK1/2 and p-P38MAPK signaling pathways, which then induced the elevated TRPC expression and enhanced SOCE and basal i in PASMCs. These works needs further evidence to elucidate in our future study. In conclusion, this study confirmed that activation of Smad1/5/8 pathway by BMP4 is dependent on BMPRII, while BMP4 induced upregulation of TRPC expression, enhancement of calcium signaling and activation of ERK1/2 and p38MAPK pathway may depend on other receptors rather than BMPRII. In clinical practice, LTBI is defined by the presence of an adaptive immune response to antigens specific for M. tuberculosis, ascertained by a positive tuberculin-skin-test or interferon-c release assay result, in the absence of active TB. According to the Infection Protection Act in Germany close contacts of TB patients are required to be subject to a TST or IGRA testing by the public health authorities.