Signaling Pathways Involved In Protease-Activated Receptor-1 Mediated Thrombin Induced Interleukin-8, MMP-2 And MMP-9 Production In Dermal Fibroblasts

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...