Hu Z-C, Tang B, Guo D, Zhang J, Liang Y-Y, Ma D, Zhu J-Y
Department of Burns, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Clin Exp Dermatol. 2014 Oct;39(7):822-8. doi: 10.1111/ced.12407. Epub 2014 Aug 22.
Keloid and hypertrophic scar (HS) are two pathological forms of excessive dermal fibrosis, which are due to aberrant wound-healing responses. Accumulating evidence suggests that aberrant activity of growth factors and increased numbers of growth factor receptors play an important role in the formation of pathological scar.
We examined the expression level of insulin-like growth factor-1 receptor (IGF-IR) in keloid, HS and normal skin.
IGF-IR expression was analyzed by immunohistochemistry, real-time PCR and western blotting on tissues and fibroblasts from 30 patients, comprising 10 patients with keloid and 20 with HS (10 with immature and 10 with mature HS), and from 10 age-matched and sex-matched healthy controls.
Immunoreactivity to IGF-IR was found in dermal fibroblasts of keloid (90%), immature HS, (80%) and mature HS (30%), but not in normal skin. There was no statistically significant difference in immunoreactivity scores between keloid and immature HS, but there was a significant difference (P < 0.01) between mature and immature HS. Real-time PCR and western blot analysis confirmed that there was high expression of IGF-IR in keloid and immature HS fibroblasts, but not in mature HS or normal skin fibroblasts. IGF-IR was expressed in the overlying epidermis, and there was no significant difference between the groups.
IGF-IR may be involved in the pathogenesis of keloid and HS. Given that IGF-IR are predominantly expressed on dermal fibroblasts, targeting of IGF-IR in fibroblasts may be of benefit to prevent scarring.
瘢痕疙瘩和增生性瘢痕(HS)是皮肤过度纤维化的两种病理形式,它们是由异常的伤口愈合反应引起的。越来越多的证据表明,生长因子的异常活性和生长因子受体数量的增加在病理性瘢痕的形成中起重要作用。
我们检测了瘢痕疙瘩、增生性瘢痕和正常皮肤中胰岛素样生长因子-1受体(IGF-IR)的表达水平。
采用免疫组织化学、实时荧光定量PCR和蛋白质印迹法,对30例患者的组织和成纤维细胞进行分析,其中包括10例瘢痕疙瘩患者、20例增生性瘢痕患者(10例未成熟增生性瘢痕和10例成熟增生性瘢痕),以及10例年龄和性别匹配的健康对照者。
在瘢痕疙瘩的真皮成纤维细胞(90%)、未成熟增生性瘢痕(80%)和成熟增生性瘢痕(30%)中发现了对IGF-IR的免疫反应性,但在正常皮肤中未发现。瘢痕疙瘩和未成熟增生性瘢痕之间的免疫反应性评分无统计学显著差异,但成熟增生性瘢痕和未成熟增生性瘢痕之间存在显著差异(P < 0.01)。实时荧光定量PCR和蛋白质印迹分析证实,IGF-IR在瘢痕疙瘩和未成熟增生性瘢痕成纤维细胞中高表达,但在成熟增生性瘢痕或正常皮肤成纤维细胞中不表达。IGF-IR在上覆表皮中表达,各组之间无显著差异。
IGF-IR可能参与瘢痕疙瘩和增生性瘢痕的发病机制。鉴于IGF-IR主要在真皮成纤维细胞上表达,靶向成纤维细胞中的IGF-IR可能有助于预防瘢痕形成。