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

Ceriani, Ricardo; Maripillan, Jaime; Ordenes, Stefany; Flores-Muñoz, Carolina; Novoa-Molina, Joel; Tapia-Bustos, Andrea; Weinstein-Oppenheimer, Caroline; Martínez, Agustín D

doi:10.3390/ijms27125155

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Open AccessArticle

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

by

Ricardo Ceriani

^1,2,*

,

Jaime Maripillan

^1,3,4,

Stefany Ordenes

^3,4,5,6,

Carolina Flores-Muñoz

^3,4,7

,

Joel Novoa-Molina

^3,4,8

,

Andrea Tapia-Bustos

²,

Caroline Weinstein-Oppenheimer

^1,9

and

Agustín D Martínez

^3,4,*

¹

Laboratorio de Innovación Terapéutica y Diagnóstico Molecular, Escuela de Química y Farmacia, Facultad de Farmacia, Universidad de Valparaíso, Valparaíso 2340000, Chile

²

Centro para la Investigación Traslacional en Neurofarmacología (CITNE), Universidad de Valparaíso, Valparaíso 2340000, Chile

³

Laboratorio de Comunicación Intercelular, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2340000, Chile

⁴

Centro Interdisciplinario de Neurociencia de Valparaíso, Instituto de Neurociencia, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2340000, Chile

⁵

Synaptopathies Laboratory, Facultad de Medicina, Universidad de Valparaíso, Valparaíso 2340000, Chile

⁶

Programa de Doctorado en Ciencias, Mención Neurociencia, Universidad de Valparaíso, Valparaíso 2340000, Chile

⁷

Facultad de Ciencias Fisiológicas, Pontificia Universidad Católica de Santiago de Chile, Santiago 8320000, Chile

⁸

Programa de Doctorado en Ciencias, Mención Biofísica y Biología Computacional, Universidad de Valparaíso, Valparaíso 2340000, Chile

⁹

Centro de Investigación, Desarrollo e Innovación en Productos Bioactivos (Cinbio), Universidad de Valparaíso, Valparaíso 2340000, Chile

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(12), 5155; https://doi.org/10.3390/ijms27125155

Submission received: 12 April 2026 / Revised: 27 May 2026 / Accepted: 5 June 2026 / Published: 6 June 2026

(This article belongs to the Special Issue Recent Advances in Wound Healing: 2nd Edition)

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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 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 alters βFGF-induced responses in human neonatal dermal fibroblasts (HDFn). Cells were treated with βFGF (10 ng/mL) in the presence or absence of PBN (200 μM), 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 βFGF-induced migration, proliferation, or most extracellular matrix-related transcriptional responses, except for a further reduction in COL1A1 expression. In addition, βFGF did not modify PANX1 transcript levels, Panx1 protein abundance, or membrane localization. Although βFGF 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 βFGF-driven regenerative responses in HDFn cells.

Keywords: pannexin-1; probenecid; βFGF; dermal fibroblasts; chronic wounds; extracellular ATP; calcium signaling; wound healing

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MDPI and ACS Style

Ceriani, R.; Maripillan, J.; Ordenes, S.; Flores-Muñoz, C.; Novoa-Molina, J.; Tapia-Bustos, A.; Weinstein-Oppenheimer, C.; Martínez, A.D. Probenecid-Mediated Pannexin-1 Inhibition Preserves βFGF-Driven Regenerative Responses in Human Dermal Fibroblasts. Int. J. Mol. Sci. 2026, 27, 5155. https://doi.org/10.3390/ijms27125155

AMA Style

Ceriani R, Maripillan J, Ordenes S, Flores-Muñoz C, Novoa-Molina J, Tapia-Bustos A, Weinstein-Oppenheimer C, Martínez AD. Probenecid-Mediated Pannexin-1 Inhibition Preserves βFGF-Driven Regenerative Responses in Human Dermal Fibroblasts. International Journal of Molecular Sciences. 2026; 27(12):5155. https://doi.org/10.3390/ijms27125155

Chicago/Turabian Style

Ceriani, Ricardo, Jaime Maripillan, Stefany Ordenes, Carolina Flores-Muñoz, Joel Novoa-Molina, Andrea Tapia-Bustos, Caroline Weinstein-Oppenheimer, and Agustín D Martínez. 2026. "Probenecid-Mediated Pannexin-1 Inhibition Preserves βFGF-Driven Regenerative Responses in Human Dermal Fibroblasts" International Journal of Molecular Sciences 27, no. 12: 5155. https://doi.org/10.3390/ijms27125155

APA Style

Ceriani, R., Maripillan, J., Ordenes, S., Flores-Muñoz, C., Novoa-Molina, J., Tapia-Bustos, A., Weinstein-Oppenheimer, C., & Martínez, A. D. (2026). Probenecid-Mediated Pannexin-1 Inhibition Preserves βFGF-Driven Regenerative Responses in Human Dermal Fibroblasts. International Journal of Molecular Sciences, 27(12), 5155. https://doi.org/10.3390/ijms27125155

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

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