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Updated: Apr 14, 2026
Isolation, Culture, and Characterization of Primary Dermal Fibroblasts from Human Keloid Tissue
Published on: July 28, 2023
The effect of suppressing discoidin domain receptor expression on keloid formation and proliferation
Yuzhi Jiang1, Xin Xing2, Shuliang Lu
1Shanghai Burn Institute, Ruijin Hospital; Shanghai Jiaotong University, Shanghai, P.R. China;
Background:
Discoidin domain receptors (DDR) with tyrosine kinase activity have been identified as novel receptors for modulating collagen production and organization in scar tissue. The purpose of this study was to explore the effect of blocking discoidin domain receptor 1 (DDR1), signaling of keloid fibroblast cells on the inhibition of keloid formation, and proliferation, by means of gene therapy.
Methods:
The expression of DDR1 in keloid tissues was investigated by immunohistology and the expression of DDR1 protein in keloid fibroblasts was examined by Western blot analysis. Keloid dermal fibroblasts were infected in vitro with modified phosphorothioate and liposome-encapsulation DDR1-antisense oligodeoxynucleotide (ASODN). Northern blot was used to analyze gene expression of DDR1 in infected keloid dermal fibroblasts and the effect on type I and type III collagen gene expression. Extracellular matrix production in infected fibroblasts was analyzed by [3H] proline incorporation.
Results:
In keloid tissues, the expression of DDR1 was observed to be widely and strongly distributed. The expression of DDR1 protein was also highly increased in keloid fibroblasts compared to normal skin fibroblasts. This was markedly downregulated in lipid-encoding DDR1-ASODN infected fibroblasts compared to lipid encoding DDR1-NSODN infected fibroblasts and lipid-infected fibroblasts. Type I and type III collagen gene expression and extracellular matrix production also were downregulated markedly in DDR1 ASODN infected fibroblasts. Moreover, the ratio of type I and type III collagen was significantly improved.
Conclusion:
An intrinsic functional difference exists between normal human dermal and keloid fibroblasts in terms of higher DDR1 gene expression in keloid fibroblasts. The quality and quantity of collagen can be improved by downregulating the expression of DDR1 using ASODN. This intervention is potentially useful in controlling fibrosis and keloid formation in clinical settings. .
Insights
Blocking discoidin domain receptor 1 (DDR1) signaling in keloid fibroblasts using gene therapy can inhibit keloid formation. This approach downregulates collagen production, improving scar quality and quantity for potential clinical use.
Area of Science:
- Dermatology and Molecular Biology
- Wound Healing and Scarring
- Gene Therapy and Fibrosis
Background:
- Discoidin domain receptors (DDRs) are tyrosine kinase receptors involved in collagen modulation in scar tissue.
- Increased DDR1 expression is observed in keloid fibroblasts, suggesting a role in keloid pathogenesis.
Purpose of the Study:
- To investigate the effect of blocking discoidin domain receptor 1 (DDR1) signaling in keloid fibroblasts.
- To evaluate the potential of gene therapy using DDR1-antisense oligodeoxynucleotide (ASODN) to inhibit keloid formation and proliferation.
Main Methods:
- Immunohistology and Western blot were used to assess DDR1 expression in keloid tissues and fibroblasts.
- Keloid fibroblasts were treated in vitro with DDR1-ASODN via liposome encapsulation.
- Northern blot and [3H] proline incorporation were employed to analyze collagen gene expression and extracellular matrix production.
Main Results:
- DDR1 expression was significantly elevated in keloid tissues and fibroblasts compared to normal skin.
- DDR1-ASODN treatment markedly downregulated DDR1, type I, and type III collagen gene expression and extracellular matrix production.
- The ratio of type I to type III collagen was significantly improved in treated fibroblasts.
Conclusions:
- Keloid fibroblasts exhibit higher DDR1 gene expression than normal dermal fibroblasts.
- Downregulating DDR1 expression with ASODN can improve collagen quality and quantity.
- This gene therapy approach shows potential for controlling fibrosis and keloid formation in clinical settings.
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