Possible involvement of SDF-1α/CXCR4-DPPIV axis in TGF-β1-induced enhancement of migratory potential in human peritoneal mesothelial cells
Possible involvement of SDF-1α/CXCR4-DPPIV axis in TGF-β1-induced enhancement of migratory potential in human peritoneal mesothelial cells
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DOI：
10.1007/s00441-007-0455-x
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发表时间：
2007-11-01
影响因子：
3.6
通讯作者：
Kikkawa, Fumitaka
中科院分区：
文献类型：
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作者：
Kajiyama, Hiroaki;Shibata, Kiyosumi;Kikkawa, Fumitaka
我们以前曾报道过，人腹膜间皮细胞（HPMCs）表达大量的二肽基肽酶IV（DPPIV），其表达受到各种生物活性物质在恶性腹水卵巢癌患者。本研究的目的是检测SDF-1 α/CXCR 4-DPPIV轴在HPMCs中的表达和作用。我们已经证明，DPPIV和E-cadherin在HPMCs的表达水平下降，TGF-β 1诱导的形态学变化，在时间和浓度依赖性的方式。此外，我们发现SDF-1 α（一种趋化因子和DPPIV底物）及其受体CXCR 4在HPMCs上表达，并且它们的表达水平通过TGF-β 1治疗上调，导致HPMCs迁移潜力增加。此外，在伤口愈合试验中，在SDF-1 α或DPPIV特异性抑制剂存在下，HPMC的迁移潜力显著增强。这些结果表明，DPPIV和SDF-1 α/CXCR 4在调节HPMCs的迁移能力中起着至关重要的作用，这可能涉及腹膜损伤部位裸露基底膜的再上皮化。
We have previously reported that human peritoneal mesothelial cells (HPMCs) express a large amount of dipeptidyl peptidase IV (DPPIV) and that its expression is regulated by a variety of bioactive substances in malignant ascites from ovarian cancer patients. The aim of this study has been to examine the expression and role of the SDF-1 alpha/CXCR4-DPPIV axis in HPMCs. We have demonstrated that the expression levels of DPPIV and E-cadherin in HPMCs decrease, following TGF-beta 1-induced morphological change, in a time- and concentration-dependent manner. Additionally, we show that both SDF-1 alpha (a chemokine and substrate for DPPIV) and its receptor, CXCR4, are expressed on HPMCs, and that their expression levels are upregulated by TGF-beta 1 treatment, resulting in an increased migratory potential of HPMCs. Furthermore, the migratory potential of HPMCs is significantly enhanced in the presence of SDF-1 alpha or DPPIV-specific inhibitor in the wound-healing assay. These results suggest that DPPIV and SDF-1 alpha/CXCR4 play crucial roles in regulating the migratory potential of HPMCs, which may be involved in the re-epithelialization of denuded basement membrane at the site of peritoneal injury.