4-HPR对瘢痕疙瘩成纤维细胞Procollagen Ⅰ、MMP-1及信号通路PI3K/Akt的影响  

The Effect of 4-hydroxyphenyl-Retinamide on Expression of Type Ⅰ Pro-collagen,MMP-1 and Signaling Pathway PI3K/Akt in Keloid Fibroblasts

作　　者：南美兰[1] 金哲虎[1] 金承龙[1] 

机构地区：[1]延边大学附属医院皮肤科,吉林延吉133000

出　　处：《中国皮肤性病学杂志》2018年第3期245-251,共7页The Chinese Journal of Dermatovenereology

基　　金：吉林省科技厅(20160101183JC);青年科研基金(2015)第31号;国家自然科学基金(81260233)

摘　　要：目的探讨4-羟苯基维胺(4-hydroxyphenyl-retinamide,4-HPR)对瘢痕疙瘩成纤维细胞的作用及PI3K/Akt信号转导通路的影响。方法通过免疫印迹方法检测人瘢痕疙瘩成纤维细胞中,4-HPR对Ⅰ型前胶原(type I pro-collagen,ProcollagenⅠ)和基质金属蛋白酶-1(matrix metallo-protein-1,MMP-1)蛋白表达水平,观察4-HPR联合TGF-β1、PD98059、SP600125、SB203580及LY294002对瘢痕疙瘩成纤维细胞中相关蛋白表达的影响。结果瘢痕疙瘩成纤维细胞中,4-HPR使ProcollagenⅠ蛋白表达水平明显减少,MMP-1蛋白表达水平明显增加,并且具有4-HPR浓度依赖性(P<0.01)。在瘢痕疙瘩成纤维细胞中,4-HPR+TGF-β1组中ProcollagenⅠ蛋白表达水平较TGF-β1组明显降低(P<0.01),但P-Smad2和P-Smad3蛋白表达均无显著改变(P>0.05)。LY294002组中ProcollagenⅠ蛋白水平与对照组相比显著降低,MMP-1显著升高(P<0.01)。但PD98059、SB203580及SP600125组中ProcollagenⅠ和MMP-1蛋白水平与对照组相比未发生明显变化(P>0.05),且4-HPR可有效抑制P-Akt蛋白表达水平(P<0.01)。结论人瘢痕疙瘩成纤维细胞中,4-HPR可以抑制Ⅰ型前胶原蛋白的表达、上调MMP-1的表达,而这种调控作用可能与PI3K/Akt信号传导通路被削弱有关。Objective To investigate the effect of 4-hydroxyphenyl-retinamide on expression of type Ⅰ pro-collagen and MMP-1 and signaling pathway PI3K/Akt in keloid fibroblasts. Methods Comparative the expression of type Ⅰ pro-collagen and MMP-1 proteins,effecting of 4-HPR therapy with Western blot in human keloid fibroblasts. The expression of related proteins was observed by 4-HPR combined with TGF-β1,PD98059,SP600125,SB203580 and LY294002 in keloid fibroblasts.Results Compared with the control group,expression of type Ⅰ pro-collagen protein decreased and MMP-1 increased of keloid fibroblastsand in the 4-HPR group,and its role showed as 4-HPR dependent of concentration（P〈0.01）. The expression of type I pro-collagen in 4-HPR＋TGF-β1 group was significantly lower than that in TGF-β1 group（P〈0.01）.However,that did not have any influenceon the expression of Phospho-Smad2and Phospho-Smad3 proteinsin keloid fibroblasts（P〉0.05）. The expression of type Ⅰ pro-collagen in LY294002 group was significantly lower than that in control group,and MMP-1 significantly increased（P〈0.01）. However,the expression of type Ⅰ pro-collagen and MMP-1 protein did not change significantly compared with the control group in PD98059,SP600125 and SB203580 group（P〉0.05）.4-HPR can effectively inhibit the expression of Phospho-Akt protein（P〈0.01）. Conclusion The data indicated that 4-HPR could suppress PI3K/Akt signal transduction pathway,which results in decreased expression of type Ⅰ pro-collagen and increased MMP-1 proteins in human keloid fibroblasts.

关 键 词：P13K/AKT信号通路 4-羟苯基维胺 Ⅰ型前胶原 瘢痕疙瘩 

分 类 号：R739.5[医药卫生—肿瘤]