Zinc-Induced PKCδ-dependent Phosphorylation of MTF-1 Promotes Pulmonary Vascular Remodeling in Hypoxic Pulmonary Hypertension.

ABSTRACT: Pulmonary hypertension (PH) is driven by pulmonary vascular remodeling, in which the zinc-sensing transcription factor metal-responsive transcription factor 1 (MTF-1) may play a pivotal regulatory role. Rodent models of hypoxia-induced PH and cultured pulmonary arterial smooth muscle cells (PASMCs) were used to investigate zinc-mediated MTF-1 activation. Phos-tag SDS-PAGE, site-directed mutagenesis, Cleavage Under Targets and Tagmentation (CUT&Tag), and pharmacological inhibitors were employed to dissect the PKCδ/MTF-1/placental growth factor (PlGF) pathway. CUT&Tag profiling revealed prominent MTF-1 enrichment at promoter regions under hypoxia, with significant occupancy at the Plgf locus and enrichment of angiogenesis-related genes. Hypoxia increased intracellular zinc levels, act

SUBMITTER: Chen A 

PROVIDER: S-EPMC12781076 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature