Hypoxia-induced TPC2 transcription and glycosylation aggravates pulmonary arterial hypertension by blocking autophagy flux.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a serious medical condition that causes a failure in the right heart. Two-pore channel 2 (TPC2) is upregulated in PAH, but its roles in PAH remain largely unknown. Our investigation aims at the mechanisms by which TPC2 regulates PAH development. We established an experimental PAH rat model via monocrotaline administration. Human and rat pulmonary arterial smooth muscle cells (PASMCs) were treated hypoxia as in vitro cell PAH models. The thickness of pulmonary arterial wall and obstructive arteriopathy in rats were examined. Autophagy was detected through TEM, and Ca²⁺ measurement and mRFP-GFP-LC3 transfection. The expression of α-SMA, LC3, p62, TPC2, HIF1α and STT3B were analyzed by qRT-PCR, western blot or IHC staining. The binding of HI

SUBMITTER: Li C 

PROVIDER: S-EPMC11682160 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature