Probenecid-Mediated Pannexin-1 Inhibition Preserves βFGF-Driven Regenerative Responses in Human Dermal Fibroblasts

Area of Science:

• Cell biology
• Wound healing research
• Pharmacology

Background:

• Chronic wounds exhibit inflammation and impaired fibroblast function, hindering tissue repair.
• Pannexin-1 (Panx1) channels influence extracellular ATP release and purinergic signaling, key in inflammation and regeneration.
• Probenecid (PBN) inhibits Panx1 channels and is explored for chronic wound therapy, but its interaction with growth factors is unknown.

Purpose of the Study:

• To investigate if Panx1 channel inhibition by PBN affects beta-fibroblast growth factor (βFGF)-induced responses in human neonatal dermal fibroblasts (HDFn).
• To assess the compatibility of PBN with regenerative processes mediated by βFGF.

Main Methods:

• HDFn cells were treated with βFGF (10 ng/mL) with or without PBN (200 μM).
• Assessed fibroblast migration, proliferation, extracellular matrix gene expression (including COL1A1), extracellular ATP release, intracellular Ca2+ signaling, and Panx1 expression/localization.

Main Results:

• PBN did not significantly alter βFGF-induced fibroblast migration, proliferation, or most extracellular matrix gene expression.
• A notable exception was PBN further reducing COL1A1 expression when combined with βFGF.
• βFGF did not affect Panx1 transcript levels, protein abundance, or membrane localization, nor did it alter the impact of PBN on extracellular ATP release and Ca2+ signaling.

Conclusions:

• Pharmacological inhibition of Panx1 channels with PBN is compatible with βFGF-driven regenerative responses in HDFn cells.
• These findings support the potential use of PBN in conjunction with growth factor therapies for chronic wound management.