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CD109 Deletion Promotes Myofibroblast Differentiation and Smad-Dependent Matrix Accumulation in Skin Fibrosis
Liqin Xu1,2, Setareh Garousi1,2, Adel Batal1,2
1Division of Plastic Surgery, Department of Surgery, McGill University, Montreal, QC H3G 1A4, Canada.
International Journal of Molecular Sciences
|March 28, 2026
Summary
Loss of CD109 in skin fibroblasts exacerbates fibrosis by enhancing transforming growth factor (TGF)-β signaling. This suggests CD109 is crucial for maintaining skin homeostasis and may be a therapeutic target for fibrotic disorders.
Area of Science:
- Dermatology
- Molecular Biology
- Fibrosis Research
Background:
- Skin fibrosis involves excessive extracellular matrix (ECM) deposition, impairing tissue function.
- Transforming growth factor (TGF)-β is a key driver of fibrotic processes.
- CD109 was previously identified as a negative regulator of TGF-β signaling and fibrotic responses.
Purpose of the Study:
- To investigate the impact of CD109 loss in dermal fibroblasts on skin fibrosis.
- To elucidate the role of CD109 in regulating TGF-β signaling and ECM production in the skin.
Main Methods:
- Utilized a bleomycin-induced skin fibrosis mouse model.
- Generated CD109 knockout (KO) mice to assess the effects of gene deficiency.
- Analyzed collagen I, fibronectin, CCN2, and α-smooth muscle actin expression via Western blotting and immunohistochemistry.
- Assessed Smad1 and Smad2/3 phosphorylation to evaluate TGF-β pathway activation.
- Performed in vitro studies using CD109 KO fibroblasts to examine migration and collagen contraction.
Main Results:
- CD109 KO mice exhibited significantly increased collagen I deposition and elevated fibronectin, CCN2, and α-smooth muscle actin levels compared to wild-type controls.
- Enhanced phosphorylation of Smad1 and Smad2/3 was observed in the skin of CD109 KO mice, indicating heightened TGF-β signaling.
- In vitro, CD109 KO fibroblasts demonstrated increased migration and collagen contraction in response to TGF-β stimulation.
- These findings collectively indicate that CD109 deficiency exacerbates dermal fibrosis.
Conclusions:
- CD109 deficiency promotes dermal fibrosis by enhancing TGF-β/Smad signaling and myofibroblast activation.
- CD109 plays a critical role in regulating skin homeostasis through modulation of ECM production and fibroblast activity.
- CD109 represents a potential therapeutic target for fibrotic disorders, including scleroderma, due to its dysregulation in these conditions.
