Expansion of CD26 positive fibroblast population promotes keloid progression
Journal Article
·
· Experimental Cell Research
- Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital (China)
- Shanghai Tissue Engineering Key Laboratory, Shanghai Jiao Tong University School of Medicine, Shanghai 200011 (China)
- Clinic for Plastic, Hand and Burns Surgery, RWTH Aachen University Hospital, 52074 Aachen (Germany)
Background: Keloid is a skin fibrosis disease that characterised by invasive growth of fibroblasts and aberrant deposition of extracellular matrix. Studies indicated that keloid fibroblasts (KFs) is a class of ‘activated’ fibroblasts, which show accelerated proliferation and excessive extracellular matrix formation as compared with normal fibroblasts (NFs). However, the mechanism underlying keloid fibroblasts dysfunction is still unknown. Objective: To verify CD26 expression difference between KFs and NFs, and investigate the function of CD26 positive fibroblasts in keloid progression. Methods: KFs and NFs were isolated from Keloid tissues and normal skin tissues respectively. Flow cytometry was performed to isolate CD26+/CD26- fibroblasts from KFs and NFs. Proliferation of different fibroblasts were analyzed by CCK8 assay and Ki 67 straining. Profibrotic phenotype difference was detected by qRT-PCR, western blot, ELISA and immunofluorescence. Scratching experiment and transwell assay were used to assess invasion ability of CD26+/CD26- fibroblasts. Diprotin A was used as a CD26 inhibitor to further investigated the function of CD26 fibroblasts in keloid disease. Result: CD26 expression was increased in KFs, and the proportion of CD26+ fibroblasts was significantly increased in KFs. Cell viability analysis showed that CD26+ fibroblasts was more active in proliferation. Furthermore, the expression of profibrotic genes were increased in CD26+ fibroblasts, including TGF-β1, IGF-1, IL6, collagen 1, collagen 3 and fibronectin. And meanwhile, CD26+ fibroblasts showed stronger invasion ability as compared to CD26- fibroblasts. Moreover, Diprotin A significantly suppressed proliferation and extracellular matrix secretion of CD26+ fibroblasts isolated from keloid tissues. Conclusion: Our findings suggest that CD26+ fibroblasts possess proliferation advantage in compare to CD26- fibroblasts, and the advantage caused expansion of CD26 positive fibroblast population promotes keloid progression.
- OSTI ID:
- 22738135
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 356; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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