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Updated: May 9, 2025
Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
CD147 inhibition reduced fibronectin expression in TGF-β1-induced keloid fibroblasts by targeting Smad2 signaling
Jian-Sheng Diao1, Hui-Cong Du1, Juan Wu1
1Department of Plastic, Aesthetic and Maxillofacial Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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.
Insights
Clusterin (CLU) is implicated in fibrosis and tumor progression. This study reveals CLU is upregulated in keloids and inhibiting it reduces keloid fibroblast activity and keloid tissue growth, suggesting CLU as a therapeutic target.
Area of Science:
- Biochemistry
- Dermatology
- Oncology
Background:
- Clusterin (CLU) is a key factor in tissue fibrosis and tumor development.
- Its specific role in keloid pathogenesis is currently unknown.
- This research investigates CLU expression and function in keloid formation.
Purpose of the Study:
- To determine the expression levels of CLU in human keloid tissues.
- To explore the functional role of CLU in keloid fibroblast (KF) activation.
- To evaluate the therapeutic potential of CLU inhibition for keloid treatment.
Main Methods:
- Immunohistopathology and western blot analysis were used to assess CLU expression in keloid tissues.
- Human keloid fibroblasts were treated with TGF-β1 and a CLU inhibitor (AC-73).
- Expression of CLU, fibronectin, and Smad2 phosphorylation was analyzed; in vivo efficacy was tested in a keloid mouse model.
Main Results:
- CLU expression was significantly elevated in keloid tissues compared to normal skin.
- TGF-β1 upregulated CLU and fibronectin in KFs; AC-73 treatment reduced these levels.
- AC-73 inhibited TGF-β1-induced fibronectin expression, Smad2 phosphorylation, and reduced keloid tissue weight in vivo.
Conclusions:
- CLU plays a significant role in keloid progression.
- Inhibiting CLU downregulates TGF-β1-induced fibronectin expression via the Smad2 pathway.
- CLU represents a potential therapeutic target for managing keloids.
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