增生性瘢痕与正常皮肤中EGFR及相关磷酸化蛋白表达差异

摘要

目的为研究增生性瘢痕的形成机制,我们对增生性瘢痕与正常皮肤表皮细胞生长因子受体(EGFR )及其相关的信号通路进行观察,包括EGFR表达、酪氨酸蛋白的磷酸化以及Stat3表达和磷酸化情况.方法所有的皮肤标本均来自烧伤后6-28个月患者的瘢痕组织以及同一病人的供皮区全层皮肤.运用免疫组化技术光镜下观察皮肤中表皮细胞生长因子受体、磷酸酪氨酸蛋白、Stat3磷酸化与非磷酸化的情况.结果增生性瘢痕与正常皮肤中的角质形成细胞表皮细胞生长因子受体和磷酸酪氨酸蛋白的表达明显不同.瘢痕组织中的表达远远高于正常组织中的表达.瘢痕组织中Stat3阳性表达明显高于正常皮肤,但其磷酸化的情况无显著差别.结论增生性瘢痕与正常组织间显示出不同的酪氨酸激酶活性,造成的信号通路差异可能是病理性瘢痕形成的机制之一.早期不同的配体刺激造成EGFR表达差异,随后导致酪氨酸蛋白磷酸化的不同,在正常的皮肤中Stat3磷酸化继续引起下游信号的表达,而瘢痕组织中Stat3磷酸化与正常情况无显著差别,造成信号不匹配.EGFR在瘢痕形成过程中扮演重要的角色.%Objective To study the potential signal pathway involved in pathogenesis of hypertrophics car formation.rnMethods The samples of scar were obtained from patients with burn wound scars 6-28 months post-burn, while the samples of normal control skin came from the donor site of the same patients. Immunohistochemistry and light microscopy techniques were used to identify the expression of epidermal growth factor receptor (EGFR) and phosphotyrosine proteins (p-Tyr), as well as the phosphorylation of signal tra nsducer and activator of transcription 3 (Stat3) in both hypertrophic scars (n=6 ) and normal skin (n=6). rnResults Significant differences were observed in the p-Tyr and EGFR positive expression keratinocytes both in hypertrophic scars and normal skin. The expression of p-Tyr, EGFR and Stat3 protein was greater in hypertrophic scars than in normal skin. However, there was no significant difference in p-Stat3 expression betwee nscar tissues and normal skin. Conclusion Different tyrosine kinase activity occurs in hypertrophic scars and normal cutan eous tissues. Initially, varied expression of EGFR is due to different ligand stimulations. However, phosphotyrosine protein and Stat3 are subsequently activa ted through phosphorylation. In scar tissues, although EGFR has an intrinsic ty rosine kinase activity when activated by EGFR correlated ligand, phosphorylation of Stat3 showed no significant changes. Therefore, cellular signal pathways are induced by EGFR, which might play arole in hypertrophic scar pathogenesis.