Abstract
Keloids occur after failure of the wound healing process; inflammation persists, and various treatments are ineffective. Keloid pathogenesis is still unclear. We have previously analysed the gene expression profiles in keloid tissue and found that HtrA1 was markedly up-regulated in the keloid lesions. HtrA1 is a serine protease suggested to play a role in the pathogenesis of various diseases, including age-related macular degeneration and osteoarthritis, by modulating extracellular matrix or cell surface proteins. We analysed HtrA1 localization and its role in keloid pathogenesis. Thirty keloid patients and twelve unrelated patients were enrolled for in situ hybridization, immunohistochemical, western blot, and cell proliferation analyses. Fibroblast-like cells expressed more HtrA1 in active keloid lesions than in surrounding lesions. The proportion of HtrA1-positive cells in keloids was significantly higher than that in normal skin, and HtrA1 protein was up-regulated relative to normal skin. Silencing HtrA1 gene expression significantly suppressed cell proliferation. HtrA1 was highly expressed in keloid tissues, and the suppression of the HtrA1 gene inhibited the proliferation of keloid-derived fibroblasts. HtrA1 may promote keloid development by accelerating cell proliferation and remodelling keloid-specific extracellular matrix or cell surface molecules. HtrA1 is suggested to have an important role in keloid pathogenesis.
Highlights
Keloids are a dermal fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) and fibroproliferation in the dermis [1,2]
To investigate role of HtrA1 in keloid pathogenesis, we examined whether HtrA1 affects cell proliferation by silencing HtrA1 gene expression using specific small interfering RNA
The addition of HtrA1 stimulated the proliferation of keloid fibroblasts, but not normal fibroblasts. These results suggest that HtrA1 plays an important role in keloid cell proliferation
Summary
Keloids are a dermal fibrotic disease characterized by abnormal accumulation of extracellular matrix (ECM) and fibroproliferation in the dermis [1,2]. They appear as raised, red, and inflexible scar tissue that develops during the wound-healing process, even from tiny wounds including vaccination and insect bites. The many treatments for keloids include steroid injections, steroid tape, and surgery with postoperative irradiation. The cure rate following surgery and postoperative radiation varies widely from 28~89% [3,5,6,7,8] and depends on the individual. Clarifying keloid pathogenesis could improve the treatment outcome
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