CD147 inhibition reduced fibronectin expression in TGF-β1-induced keloid fibroblasts by targeting Smad2 signaling pathway

Background: CD147 is closely involved in the progression of fibrosis and tumor formation in various tissues, however, its role in keloid formation remains unknown. In this study, we investigate the expression of CD147 in keloids and explore its functional roles. Methods: CD147 expression in human keloid tissues was assessed using immunohistopathology and western blot analysis. Human keloid fibroblasts (KFs) were cultured and treated with TGF-β1 alone or in combination with the CD147 inhibitor AC-73. Western blot and immunofluorescence were employed to examine CD147 and fibronectin expression levels in KFs post-treatment. Additionally, the effect of CD147 inhibitor on Smad2 phosphorylation and fibronectin protein levels in TGF-β1-induced KFs was evaluated by western blot. Finally, a keloid-bearing nude mouse model was established to investigate the therapeutic effect of AC-73 in vivo. Results: CD147 expression was significantly higher in keloid tissues compared to normal skin. TGF-β1 treatment upregulated CD147 and fibronectin expressions in cultured KFs. Inhibition of CD147 with AC-73 reduced the expression levels of both CD147 and fibronectin in KFs. Additionally, AC-73 markedly attenuated TGF-β1-induced fibronectin expression and suppressed Smad2 phosphorylation. In the nude mouse model, AC-73 significantly reduced the gross weight of xenotransplanted keloid tissues. Conclusion: These findings suggest that CD147 is closely involved in keloid progression. Inhibition of CD147 downregulates TGF-β1-induced fibronectin expression in KFs by targeting Smad2 signaling pathway. Thus, CD147 may serve as a promising therapeutic target for keloid treatment.