Abstract

Chronic wounds are characterized by persistent inflammation and impaired fibroblast function, leading to defective tissue repair. Pannexin-1 (Panx1) channels regulate extracellular ATP release and purinergic signaling, processes implicated in inflammation and regeneration. Probenecid (PBN), a clinically approved Panx1 channels inhibitor, has emerged as a potential therapeutic modulator in chronic wounds; however, its compatibility with growth factor-mediated regenerative responses remains unclear. Here, we evaluated whether pharmacological inhibition of Panx1 channels alters beta FGF-induced responses in human neonatal dermal fibroblasts (HDFn). Cells were treated with beta FGF (10 ng/mL) in the presence or absence of PBN (200 mu M), and migration, proliferation, extracellular matrix-related gene expression, extracellular ATP release, intracellular Ca2+ signaling, and Panx1 expression/localization were assessed. PBN did not significantly alter beta FGF-induced migration, proliferation, or most extracellular matrix-related transcriptional responses, except for a further reduction in COL1A1 expression. In addition, beta FGF did not modify PANX1 transcript levels, Panx1 protein abundance, or membrane localization. Although beta FGF reduced extracellular ATP release and transiently modulated ATP-induced Ca2+ signaling, these effects occurred without detectable changes in Panx1 expression or localization. These findings support the compatibility of PBN with beta FGF-driven regenerative responses in HDFn cells.