Comprehensive identification of signaling pathways foridiopathic pulmonary arterial hypertension.

Comprehensive identification of signaling pathways foridiopathic pulmonary arterial hypertension. Am J Physiol Cell Physiol. 2020 Mar 11;: Authors: Liu B, Zhu L, Yuan P, Marsboom G, Hong Z, Liu J, Zhang P, Hu Q Abstract Whole exome sequencing (WES) was used in the research of familial pulmonary arterial hypertension (FPAH). CAV1 and KCNK3 were found as two novel candidate genes of FPAH. However, few pathogenic genes were identified in idiopathic pulmonary arterial hypertension (IPAH). We conducted WES in 20 unrelated IPAH patients that did not carry the known PAH-pathogenic variants among BMPR2, CAV1, KCNK3, SMAD9, ALK1 and ENG. We found a total of 4950 variants in 3534 genes including 4444 SNPs and 506 InDels. Through the comprehensive and multi-level analysis, we disclosed several novel signaling cascades significantly connected to IPAH, including variants related to cadherin signaling pathway, dilated cardiomyopathy, glucose metabolism, immune response, mucin-type O-glycosylation, PLC-activating GPCR signaling pathway, vascular contraction and generation, and voltage-dependent Ca2+ channels. We also conducted validation studies in five mutant genes related to PLC-activating GPCR signaling pathway potentially involved in intracellular calcium regulation through Sanger sequencing for mutation accuracy, qRT-PCR for mRNA stability, immunofluorescence for subcellular localization, western blot for protein level, fura-2 imaging for intr...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Tags: Am J Physiol Cell Physiol Source Type: research