凝血酶激活真皮成纤维细胞蛋白酶激活受体-1释放白细胞介素-8及金属蛋白酶的信号通路研究
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摘要
人类真皮成纤维细胞是一重要组成细胞，它广泛分布于机体。在炎症过程和创伤修复方面的作用日益受到重视。蛋白酶激活受体(Protease-activated receptors，PARs)属G蛋白偶联受体家族成员，广泛分布在各种类型的细胞膜上。不同亚型的蛋白酶活性受体在不同来源的成纤维细胞中表达不同。成纤维细胞可分泌IL-8，炎症趋化因子，在系统性红斑狼疮、类风湿性关节炎和组织缺氧时都发现IL-8的表达增加，这一前炎症因子在皮肤炎症和纤维化中起重要作用。
金属蛋白酶，在胚胎发育和形态变化、繁殖、组织再吸收和重塑、肿瘤侵润和代谢中起作用。成纤维细胞丰富存在于结缔组织，因此血管损伤部位的凝血因子与这些细胞接触。真皮成纤维细胞不仅产生组织皮肤的细胞外基质，也与其他细胞相互作用，主要调节皮肤生理功能。
目前对于真皮成纤维细胞蛋白酶激活受体及各亚型受体的表达、激活作用以及产生的效应物研究较少，对凝血酶作用于成纤维细胞的PAR和激活受体后所参与的信号通路和生物学作用均知之甚少。
本研究目的就是探索真皮成纤维细胞的PAR各亚型的表达状态，凝血酶激
Dermal fibroblasts not only produce and organize the extracellular matrix of the dermis but they also communicate with each other and other cell types, playing a crucial role in regulating skin physiology and pathology. The role of fibroblasts in inflammatory processes and wound remodeling is increasingly being recognized. Protease-activated receptors (PARs) have wide diverse cell types tissues distribution. Different subtypes of PARs have been expressed on fibroblasts from different source. It was reported that thrombin could induce IL-8 secretion from human dermal fibroblasts (HDFs) through activation of proteinase activated receptor (PAR)-1. However, little is known of intracellular signaling pathways involved in the event. Our aim was to explore the capacity of dermal fibroblasts to produce MMP-2, MMP-9 and inflammatory chemokine IL-8 invovled in thrombin stimulation via PAR. We also revealed which intracellular signal pathway was involved in this process.
Here we determined the subtypes of PARs that were expressed on the human dermal fibroblast by immunostaining, FCM and RT-PCR. Furthermore we examined
金属蛋白酶，在胚胎发育和形态变化、繁殖、组织再吸收和重塑、肿瘤侵润和代谢中起作用。成纤维细胞丰富存在于结缔组织，因此血管损伤部位的凝血因子与这些细胞接触。真皮成纤维细胞不仅产生组织皮肤的细胞外基质，也与其他细胞相互作用，主要调节皮肤生理功能。
目前对于真皮成纤维细胞蛋白酶激活受体及各亚型受体的表达、激活作用以及产生的效应物研究较少，对凝血酶作用于成纤维细胞的PAR和激活受体后所参与的信号通路和生物学作用均知之甚少。
本研究目的就是探索真皮成纤维细胞的PAR各亚型的表达状态，凝血酶激
Dermal fibroblasts not only produce and organize the extracellular matrix of the dermis but they also communicate with each other and other cell types, playing a crucial role in regulating skin physiology and pathology. The role of fibroblasts in inflammatory processes and wound remodeling is increasingly being recognized. Protease-activated receptors (PARs) have wide diverse cell types tissues distribution. Different subtypes of PARs have been expressed on fibroblasts from different source. It was reported that thrombin could induce IL-8 secretion from human dermal fibroblasts (HDFs) through activation of proteinase activated receptor (PAR)-1. However, little is known of intracellular signaling pathways involved in the event. Our aim was to explore the capacity of dermal fibroblasts to produce MMP-2, MMP-9 and inflammatory chemokine IL-8 invovled in thrombin stimulation via PAR. We also revealed which intracellular signal pathway was involved in this process.
Here we determined the subtypes of PARs that were expressed on the human dermal fibroblast by immunostaining, FCM and RT-PCR. Furthermore we examined
引文
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