Suppressed inflammatory gene expression during human hypertrophic scar compared to normotrophic scar formation.
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 (HTscar) and not to normotrophic scar (NTscar) 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 HTscar and six patients who developed NTscar. It was found that HTscar formation coincided with a prolonged decreased expression of inflammatory genes (TNFα, IL-1α, IL-1RN, CCL2, CCL3, CXCL2, CXCR2, C3 and IL-10) and an extended increased expression of ECM-related genes (PLAU, Col3A1, TGFβ3). This coincided with a delayed but prolonged infiltration of macrophages (type 2) in HTscar tissue compared to NTscar 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.
Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands.|Research Institute MOVE, Amsterdam, The Netherlands.|A-SKIN Nederland BV, Amsterdam, The Netherlands.
Lenie J
LJ
van den Broek
Department of Plastic Reconstructive and Hand Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Willem M
WM
van der Veer
Department of Plastic and Reconstructive Surgery, University Medical Center Groningen, Groningen, The Netherland.
Etty H
EH
de Jong
Department of Dermatology, VU University Medical Center, Amsterdam, The Netherlands.|Research Institute MOVE, Amsterdam, The Netherlands.|Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands.
Susan
S
Gibbs
Research Institute MOVE, Amsterdam, The Netherlands.|Department of Plastic Reconstructive and Hand Surgery, VU University Medical Center, Amsterdam, The Netherlands.
Frank B
FB
Niessen
D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics; D042501:Angiogenic Proteins / Q000096:biosynthesis / Q000235:genetics*; D001706:Biopsy; D002921:Cicatrix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017439:Cicatrix, Hypertrophic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000235:genetics; D011183:Postoperative Complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D056346:Sternotomy; D014945:Wound Healing / Q000235:genetics*
D048948:14-3-3 Proteins; D042501:Angiogenic Proteins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; C572235:YWHAZ protein, human
human; hypertrophic; inflammation; normotrophic; scar