过度增生性瘢痕骨膜蛋白与转化生长因子-β1的表达

Expression of periostin and transforming growth factor-β1 in hypertrophic scar

目的探讨过度增生性瘢痕(瘢痕疙瘩)组织中骨膜蛋白(periostin)的表达与转化生长因子-β1(TGF-β1)和受体的关系。方法选择从2019年2月~2021年10月于首都医科大学附属北京朝阳医院整形外科接受整形手术的患者66例,包括瘢痕疙瘩24例,增生性瘢痕22例,正常皮肤20例。采用实时荧光定量聚合酶链式反应(RT-PCR)法检测上述三种组织中periostin、TGF-β1和受体信使RNA(mRNA)表达,并行Pearson相关性分析。此外,采用流式细胞术完成上述组织基质金属蛋白酶(MMP)-2以及MMP-9表达水平,以Pearson相关分析明确其和periostin、TGF-β1 mRNA表达的关系。此外,比较不同皮肤组织超氧化物歧化酶(SOD)、丙二醛(MDA)以及AOPP表达水平,组间比较采用t检验。结果瘢痕疙瘩组织中periostin、TGF-β1及TGF-βRⅠmRNA相对表达量高于增生性瘢痕以及正常组织(0.94±0.25比0.94±0.25、0.50±0.14;0.55±0.12比0.31±0.10、0.20±0.05;0.72±0.23比0.35±0.11、0.20±0.05,t=3.309、6.939、7.392、11.094、7.055、9.890,P<0.05);且增生性瘢痕组织上述指标mRNA相对表达量均高于正常组织(0.94±0.25比0.50±0.14;0.31±0.10比0.20±0.05;0.35±0.11比0.20±0.05,t=4.142、3.527、5.625,P<0.05)。经Pearson相关性分析发现,periostin与TGF-β1、TGF-βRⅠ均呈正相关关系(r=0.623、0.571,P<0.05)。瘢痕疙瘩组织MMP-2以及MMP-9表达水平低于增生性瘢痕组织以及正常组织(0.76±0.16比0.82±0.18、1.01±0.21;0.69±0.12比0.80±0.15、1.02±0.24);且增生性瘢痕组织MMP-2以及MMP-9表达水平低于正常组织(0.82±0.18比1.01±0.21;0.80±0.15比1.02±0.24,F=7.495、10.394,P<0.01)。经Pearson相关性分析可得,periostin、TGF-β1与MMP-2、MMP-9表达均呈负相关(r=-0.501、-0.489;-0.574、-0.523,P<0.05)。瘢痕疙瘩组织中SOD、MDA以及AOPP表达水平均高于增生性瘢痕、正常组织(51.32±8.13比45.28±6.23、35.19±5.94;6.88±1.25比5.12±0.74、3.15±0.46;59.47±10.36比50.78±8.34、41.75±6.81);且增生性瘢痕上述各项指标表达水平均高于正常组织(45.28±6.23比35.19±5.94;5.12±0.74比3.15±0.46;50.78±8.34比41.75±6.81,F=12.305、9.378、15.287,P<0.01)。结论瘢痕疙瘩组织中periostin异常高表达,且和TGF-β1及其受体密切相关,可能在瘢痕疙瘩形成过程中起着至关重要的作用。

Objective To study the relationship between periostin expression and transforming growth factor-β1(TGF-β1)and its receptors in hypertrophic scar(keloid)tissue.Methods From February 2019 to October 2021,66 patients who received plastic surgery in the Department of Plastic Surgery,Beijing Chaoyang Hospital Affiliated to Capital Medical University were selected,including 24 cases of keloid,22 cases of hypertrophic scar and 20 cases of normal skin.Real-time fluorescence quantitative polymerase chain reaction(RT-PCR)was used to detect the mRNA expression of periostin,TGF-β1 and receptor in the above three tissues,and Pearson correlation analysis was performed.In addition,flow cytometry was used to detect the expression levels of matrix metalloproteinase-2(MMP-2)and MMP-9 in the above tissues,and Pearson correlation analysis was used to clarify the relationship between the mRNA expression of periostin and TGF-β1.The expression levels of superoxide dismutase(SOD),malondialdehyde(MDA)and AOPP in different skin tissues were compared.The SPSS 22.0 software was used to analyze the results of this paper.Results The relative expression levels of periostin,TGF-β1 and TGF-βRⅠmRNA in keloid tissue were higher than those in hypertrophic scar and normal tissue(0.94±0.25 vs.0.94±0.25,0.50±0.14;0.55±0.12 vs.0.31±0.10,0.20±0.05;0.72±0.23 vs.0.35±0.11,0.20±0.05,t=3.309,6.939;7.392,11.094;7.055,9.890,P<0.05).The mRNA relative expression levels of above indexes in hypertrophic scar tissue were higher than those in normal tissue(0.94±0.25 vs.0.50±0.14;0.31±0.10 vs.0.20±0.05;0.35±0.11 vs.0.20±0.05,t=4.142,3.527,5.625;P<0.05).Pearson correlation analysis showed that periostin was positively correlated with TGF-β1 and TGF-βRⅠ(r=0.623,0.571,P<0.05).The expression levels of MMP-2 and MMP-9 in keloid tissue were lower than those in hypertrophic scar tissue and normal tissue(0.76±0.16 vs.0.82±0.18 and 1.01±0.21;0.69±0.12 vs.0.80±0.15 and 1.02±0.24).The expression levels of MMP-2 and MMP-9 in hypertrophic scar tissue were lower than those in normal tissue(0.82±0.18 vs.1.01±0.21;0.80±0.15 vs.1.02±0.24,F=7.495,10.394,P<0.01).Pearson correlation analysis showed that periostin and TGF-β1 were negatively correlated with the expression of MMP-2 and MMP-9(r=-0.501,-0.489;-0.574,-0.523,P<0.05).The expression levels of SOD,MDA and AOPP in keloid tissue were higher than those in hypertrophic scar and normal tissue(51.32±8.13 vs.45.28±6.23,35.19±5.94;6.88±1.25 vs.5.12±0.74,3.15±0.46;59.47±10.36 vs.50.78±8.34,41.75±6.81).The expression levels of the above indexes in hypertrophic scar were higher than those in normal tissue(45.28±6.23 vs.35.19±5.94;5.12±0.74 vs.3.15±0.46;50.78±8.34 vs.41.75±6.81,F=12.305,9.378,15.287,all P<0.01).Conclusion The abnormally high expression of periostin in keloid tissues is closely related to TGF-β1 and its receptors,which may play an important role in the formation of keloid.