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Suppressed inflammatory gene expression during human hypertrophic scar compared to normotrophic scar formation
Author(s) -
Broek Lenie J.,
Veer Willem M.,
Jong Etty H.,
Gibbs Susan,
Niessen Frank B.
Publication year - 2015
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.12739
Subject(s) - hypertrophic scar , wound healing , infiltration (hvac) , inflammation , extracellular matrix , scar tissue , pathology , medicine , angiogenesis , granulation tissue , gene expression , immunohistochemistry , gene , immunology , biology , microbiology and biotechnology , surgery , cancer research , biochemistry , physics , thermodynamics
Abstract Hypertrophic scar formation is a result of adverse cutaneous wound healing. The pathogenesis of hypertrophic scar formation is still poorly understood. A problem next to the lack of suitable animal models is that often normal skin is compared to hypertrophic scar ( HT scar) and not to normotrophic scar ( NT scar) tissue. Another drawback is that often only one time period after wounding is studied, while scar formation is a dynamic process over a period of several months. In this study, we compared the expression of genes involved in inflammation, angiogenesis and extracellular matrix ( ECM ) formation and also macrophage infiltration in biopsies obtained before and up to 52 weeks after standard surgery in five patients who developed HT scar and six patients who developed NT scar. It was found that HT scar formation coincided with a prolonged decreased expression of inflammatory genes ( TNF α , IL ‐1 α , IL ‐1 RN , CCL 2, CCL 3, CXCL 2, CXCR 2, C3 and IL ‐10) and an extended increased expression of ECM ‐related genes ( PLAU , Col3A1, TGF β 3). This coincided with a delayed but prolonged infiltration of macrophages (type 2) in HT scar tissue compared to NT scar tissue. These findings were supported by immunohistochemical localization of proteins coding for select genes named above. Our study emphasizes that human cutaneous wound healing is a dynamic process that is needed to be studied over a period of time rather than a single point of time. Taken together, our results suggest innate immune stimulatory therapies may be a better option for improving scar quality than the currently used anti‐inflammatory scar therapies.