GOLPH3 regulates fibronectin production via TGF-β/SMAD signaling in dermal fibroblasts.

Golgi phosphoprotein 3 (GOLPH3) has been implicated in diverse cellular processes; however, its role in extracellular matrix (ECM) regulation during cellular senescence remains unclear. In this study, we investigated the function of GOLPH3 in human dermal fibroblasts. Ultraviolet A (UVA) irradiation and hydrogen peroxide (H2O2) treatment significantly reduced GOLPH3 protein levels, accompanied by decreased levels of collagen type I alpha 1 (COL1A1) and fibronectin, while p53 protein levels were increased. Similarly, replicative senescence resulted in reduced GOLPH3 and fibronectin levels. Knockdown of GOLPH3 using a recombinant adenovirus expressing microRNA targeting GOLPH3 markedly decreased fibronectin production, with minimal effects on collagen type I alpha 1, and increased p53 protein levels. Furthermore, GOLPH3 depletion attenuated TGF-β-induced ECM production and significantly suppressed SMAD2/3 phosphorylation. In contrast, Overexpression of GOLPH3 did not significantly alter ECM protein levels under basal condition. Overexpression of p53 reduced ECM protein levels without altering GOLPH3 protein levels, and co-knockdown experiments indicated that fibronectin reduction induced by GOLPH3 depletion occurs largely independently of p53. Collectively, these findings demonstrate that GOLPH3 plays a critical role in fibronectin production by modulating TGF-β/SMAD signaling in dermal fibroblasts, with a limited contribution from p53-associated pathways.