人角质形成细胞Notch信号通路与转化生长因子β调控受体蛋白的作用☆◆

摘要

背景：在皮肤中受体蛋白酪氨酸磷酸酶kappa的调控至关重要，而转化生长因子β似乎是其调控的上游因子，既然Notch信号和转化生长因子β信号通道如此相关，那么Notch是不是也参加了转化生长因子β信号对受体蛋白酪氨酸磷酸酶kappa的调控呢？目的：探讨 Notch 信号通道在人角质形成细胞中对转化生长因子β调控受体蛋白酪氨酸磷酸酶 kappa的作用的影响。方法：在分别用Jagged-1激活和用Γ-分泌酶抑制剂抑制Notch信号通道后，加入转化生长因子β，同时设立对照组，用Real-time PCR测试人角质形成细胞中受体蛋白酪氨酸磷酸酶kappa mRNA表达量。结果与结论：覆盖率为40%的角质形成细胞在加入了转化生长因子β后，受体蛋白酪氨酸磷酸酶kappa mRNA 量在各时间点均高于对照组。在用 Jagged-1激活 Notch 通道的角质形成细胞中，单独加入Jagged-1、转化生长因子β及两者都加入时均高于对照组(P<0.05，P<0.01)。在用γ-分泌酶抑制剂抑制Notch通道的角质形成细胞中，只加入转化生长因子β显著高于对照组(P<0.01)，只加入γ-分泌酶抑制剂和两者均加入时与对照组比较，差异无显著性意义(P >0.05)。说明加入转化生长因子β导致角质形成细胞中受体蛋白酪氨酸磷酸酶kappa表达增加，而分别对Notch信号进行激活和抑制后发现，受体蛋白酪氨酸磷酸酶kappa信号分别显著增加和显著被抑制。所以在转化生长因子β升高受体蛋白酪氨酸磷酸酶kappa表达过程中Notch信号通道是非常重要且不可或缺的。%BACKGROUND:Regulation of the receptor protein tyrosine phosphatase kappa (RPTP-κ) in the skin is essential, while transforming growth factor beta (TGF-β) appears to be an upstream factor of its regulation. As Notch signaling pathway is similar to TGF-βsignaling pathway, whether Notch participates in the regulation of RPTP-κtranscription by TGF-βsignaling? OBJECTIVE:To find out the role of Notch signal in regulation of RPTP-κtranscription by TGF-β. METHODS:Jagged-1 and gamma-secretase inhibitors (GSI) were use respectively to activate and inhibit Notch signal fol owed by addition of TGF-β. Simultaneously, control group was set. Real-time PCR was used to determine RPTP-k mRNA expression in human keratinocytes. RESULTS AND CONCLUSION:After adding TGF-βinto 40%confluent keratinocytes, the RPTP-κmRNA expression was higher at different time as compared with the control group. Fol owing Jagged-1 activated Notch signaling pathway, the mRNA expression of RPTP-κin the keratinocytes was higher when Jagged-1, TGF-βor their combination was added into the cel s as compared with the control group (P<0.05, P<0.01). Fol owing GSI inhibited Notch signaling pathway, the mRNA expression of RPTP-κin the keratinocytes was higher only when TGF-βwas added into the cel s as compared with the control group (P<0.01), and no significant difference was seen when GSI alone or combination of TGF-βand GSI was added into the cel s as compared with the control group (P>0.05). These findings indicate that the mRNA expression of RPTP-κin the keratinocytes was increased after TGF-βwas added, and fol owing activation or inhibition of Notch signaling, the mRNA expression of RPTP-κwas significantly increased or suppressed. Therefore, Notch signaling is very important and indispensable in the regulation of RPTP-κby TGF-β.