1331 Regulation of fibronectin production by Golgi phosphoprotein 3 (GOLPH3) in dermal fibroblasts

Golgi phosphoprotein 3 (GOLPH3) is a peripheral membrane protein of the Golgi stack and is responsible for functions such as vesicle trafficking, protein glycosylation, and maintenance of Golgi conformation. However, the role of GOLPH3 in the production of extracellular matrix (ECM) in dermal fibroblasts is not well understood. In this study, we investigated the expression of GOLPH3 and its role in ECM production. Treatment of fibroblasts with UVA and hydrogen peroxide resulted in the induction of cellular senescence as evidenced by increases in p53 and p21. On the other hand, the production of ECM, such as collagen and fibronectin, was inhibited by UVA and hydrogen peroxide. The expression of GOLPH3 was also decreased under this cellular senescence condition, indicating a possible role of GOLPH3 in ECM production in fibroblasts. We transduced fibroblasts with a recombinant adenovirus expressing a microRNA (miR) targeting GOLPH3 to downregulate its expression. As a result, the downregulation of GOLPH3 significantly reduced fibronectin levels, while slightly affecting collagen levels. In contrast, GOLPH3 overexpression did not affect the levels of fibronectin and collagen in fibroblasts. Interestingly, the downregulation of GOLPH3 resulted in an increase of p53 and a decrease of SMAD3. These results suggest that GOLPH3 is downregulated during cellular senescence and negatively affects fibronectin levels by regulating p53 and SMAD in dermal fibroblasts.