Pannexin 1 drives cardiac fibroblast activation and fibrosis via the ATP-purinergic receptor-JAK2/STAT3 axis in heart failure.
TL;DR
In vivo injection of a PANX1 blocker provides evidence for the role of Panx1 in alleviating cardiac fibrosis and bioinformatics analysis suggests that this process is associated with the JAK/STAT signaling pathway.
Abstract
Pannexin 1 (PANX1), a member of the gap junction protein family, is ubiquitously expressed across various tissues and plays a key role in ATP release and signal transduction. In this study, we investigate Panx1 expression in cardiac fibroblasts under pathological conditions, specifically focusing on heart failure. Transcriptomic analysis reveals that Panx1 expression is upregulated in mouse hearts after transverse aortic constriction (TAC) surgery. Single-cell sequencing data from TAC mice indicate that Panx1 is predominantly expressed in fibroblasts, and its expression is significantly elevated in TAC mice. The upregulation of the PANX1 protein in fibroblasts following TAC is further corroborated by immunofluorescence staining and western blot analysis. Similarly, single-cell sequencing data from human heart failure patients are consistent with those from TAC mice, showing high PANX1 expression in fibroblasts. Pathway enrichment analysis of fibroblasts with differential Panx1 expression reveals that the JAK/STAT signaling pathway is commonly enriched in both species. In vitro knockdown and overexpression of the Panx1 gene are used to demonstrate its effect on the fibroblast phenotype. In vivo injection of a PANX1 blocker provides evidence for the role of Panx1 in alleviating cardiac fibrosis. The PANX1 channel is expressed in cardiac fibroblasts and is upregulated after TAC. Bioinformatics analysis suggests that this process is associated with the JAK/STAT signaling pathway. The Panx1 gene regulates phenotypic changes in fibroblasts and activates the downstream JAK/STAT signaling pathway via the ATP-purinergic receptor.