Extracellular ATP activates nuclear translocation of ERK1/2 leading to the induction of matrix metalloproteinases expression in human endometrial stromal cells

Abstract

ATP has been shown to activate the mitogen-activated protein kinase (MAPK) signaling pathway in various systems. However, little is known about the signaling events and the effects in human endometrial stromal cells (hESCs). The present study examined the effect of ATP on activating MAPKs and its subsequent events in hESCs. This study demonstrated the expression of the P 2U /P2Y 2 receptor in hESCs by reverse transcription-PCR (RT-PCR). A PCR product with a sequence identical to the reported 599 bp P 2U /P2Y 2 receptor cDNA was obtained. Western blot analysis, using a monoclonal antibody against the phosphorylated forms of ERK1/2, demonstrated that ATP activated MAPK in a dose-and time-dependent manner. Confocal microscopy showed an evident nuclear translocation of phosphorylated ERKs after 10 mM ATP treatment, but this effect was blocked by PD98059. To study the gene(s) induced by exogenous ATP, mRNA was extracted from hESCs in the presence or absence of 10 mM ATP. The gene array for 96 genes associated with members of human matrix metalloproteinases (MMPs) and adhesion molecules revealed that the expression of MMP-2, -3, -10, and -24 genes was increased and the effect was attenuated by PD98059. Furthermore the effects of ATP on the expression of MMP genes were confirmed by semiquantitative RT-PCR. To our knowledge, this is the first demonstration of the ATP-induced nuclear translocation of phospho-ERK1/2 that mediates MMPs gene expression in human endometrial cells. These results support the notion that the ERK1/2 signaling pathway is involved in mediating ATP actions in the human reproductive system.

IL-1β Promotes Corneal Epithelial Cell Migration by Increasing MMP-9 Expression through NF-κB- and AP-1-Dependent Pathways

“…2E). Extracellular ATP activates nuclear translocation of ERK1/2 leading to the induction of MMPs expression in human endometrial stromal cells [21]. Thus, we also observed whether IL-1β could stimulate p42/p44 MAPK translocation.…”

TNF-α induces cytosolic phospholipase A2expression via Jak2/PDGFR-dependent Elk-1/p300 activation in human lung epithelial cells

“…5, A and B, TNF-␣ markedly induced Akt translocation from the cytosol into the nucleus in a time-dependent manner. Extracellular ATP activates nuclear translocation of p42/p44 MAPK, leading to the induction of matrix metalloproteinase expression in human endometrial stromal cells (6). In this study, we also observed that TNF-␣ induced p42/p44 MAPK translocation from the cytosol into the nucleus in a time-dependent manner (Fig.…”

“…Akt phosphorylation is essential for nuclear translocation and retention (41). Extracellular ATP activates nuclear translocation of p42/p44 MAPK, leading to the induction of matrix metalloproteinase expression in human endometrial stromal cells (6). Here, we also demonstrated that TNF-␣ markedly induced Akt and p42/p44 MAPK translocation, which was mediated through a Jak2/PDGFR/PI3K pathway in HPAEpiCs.…”

LRIG1 modulates aggressiveness of head and neck cancers by regulating EGFR-MAPK-SPHK1 signaling and extracellular matrix remodeling

“…Interestingly, the level of TIMP2, an MMP inhibitor, was significantly increased ( Figure 4b). As phospho-MAPK (pMAPK) can be translocated into cell nucleus and act as a transcriptional regulator, 26 we examined whether pMAPK was directly responsible for reduced expression of LRIG1 targets. Chromatin immunoprecipitation (ChIP) analysis with anti-pMAPK antibodies revealed that LRIG1 induction significantly attenuates binding of pMAPK-associated transcription factors to promoter regions of MMP-1, MMP-3 and MMP-10 ( Figure 4c).…”