TG2 (transglutaminase 2) promotes PINK1/Parkin-dependent mitophagy in pulmonary hypertension by regulating the TRPC6 - PubMed
a day ago
- #TRPC6
- #pulmonary hypertension
- #mitophagy
- TG2 (transglutaminase 2) is upregulated in pulmonary hypertension (PH) patients, HPH mice, and hypoxia-induced human pulmonary smooth muscle cells (hPSMCs).
- TG2 deficiency in hPSMCs reduces TRPC6 protein levels and calcium activity, suggesting TRPC6 as a novel target for TG2 regulation.
- TG2 knockdown decreases mitophagy proteins PINK1, Parkin, and LC3, while increasing p62/SQSTM, inhibiting mitophagy flux under hypoxia.
- TG2 deficiency increases mitochondrial reactive oxygen species (ROS) and impedes mitochondrial membrane depolarization.
- TG2 activation promotes hyper-proliferation and anti-apoptotic phenotypes in hPSMCs via mitophagy during mitochondrial dysfunction.
- TG2 regulates TRPC6 expression through serotonylation, linking TG2 to mitochondrial function and HPH progression.
- The study identifies TG2 as a potential therapeutic target for hypoxia pulmonary hypertension (HPH).