Identification of a novel mutation in the mechanoreceptor-encoding gene CXCR1 in patients with keloid

Qiguo Zhang,Xiaoyan Zhao,Liangqi Cai,Yijin Huang,Xiaoping Ke,Mian Wang

doi:10.1007/s00403-018-1847-3

Qiguo Zhang, Xiaoyan Zhao + Show 4 more

Open Access

https://doi.org/10.1007/s00403-018-1847-3

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Abstract

Keloids are skin fibroproliferative tumors characterized by locally invasive growth of fibroblasts and excessive collagen deposition. The objective of this study is to investigate the molecular basis of the keloid scar by studying the mutation of related genes. We performed gene screening of mechanoreceptors by quantitative polymerase chain reaction (qPCR), Sanger sequencing to detect the CXCR1gene mutation, and immuno-histochemistry to determine CXCR1 protein expression. Among the genes encoding mechanoreceptors, the expression of CXCR1 mRNA was significantly higher in keloid scar tissues than in the surrounding tissues of normal controls (P < 0.05). Sequencing analysis identified a novel missense mutation, c.574G > A (p.Gly192Glu). Immunohistochemistry showed heightened protein expression of CXCR1 in keloid scars as compared to controls. Our findings indicate that CXCR1 gene mutation and altered protein expression are associated with keloid scar development. Identification of the CXCR1 gene mutation might provide insights into the molecular mechanism underlying keloid scar and underscores the potential importance of mechanoreceptors in keloid scar pathogenesis.

Highlights

Keloid is a dermal fibroproliferative tumor that forms at the site of a cutaneous injury and is characterized by heterogeneity, excessive collagen accumulation and locally aggressive invasion [9]
Ogawa et al reported that keloid and hypertrophic scars in the reticular dermis result from chronic inflammation [12], which favors the possibility that a primary inflammatory lesion may facilitate the formation of keloid, which suggests that mechanical tension plays a potentially important role in the development of keloid
Considering potential involvement of mechanical tension in the keloid, we analyzed the expression of some known mechanoreceptor-encoding genes, including CXCR1, CXCR2, TGFBR1, TGFBR2, ITGA2, ITGB1, LRP5, FZD4, FZD7, RFTN1, and TNFR1

Summary

Introduction

Keloid is a dermal fibroproliferative tumor that forms at the site of a cutaneous injury and is characterized by heterogeneity, excessive collagen accumulation and locally aggressive invasion [9]. The excessive deposition of fibroblast-derived collagens I and III in the growing margin of keloid scars as compared to intralesional and extralesional sites [15] greatly concern patients physically, psychologically and cosmetically [1, 19]. Keloids at chest areas and the lower extremities are most vulnerable to recur even after completion of successful treatment [13], which implicates that high mechanical tension actively contributes to keloid. Keloids tend to develop at high-tension sites such as the chest, back, and extremities. Ogawa et al reported that keloid and hypertrophic scars in the reticular dermis result from chronic inflammation [12], which favors the possibility that a primary inflammatory lesion may facilitate the formation of keloid, which suggests that mechanical tension plays a potentially important role in the development of keloid

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