Cyclooxygenase-2 regulates HPS patient serum induced-directional collective HPMVEC migration via PKC/Rac signaling pathway.
Hepatopulmonary syndrome (HPS) is a serious complication in patients with advanced liver disease. The pathological pulmonary angiogenesis contributes to the progression of HPS. Importantly, directional collective migration of endothelial cells is a critical event for pathological angiogenesis. Previously, we have demonstrated that the over-expression of Cyclooxygenase-2 (COX-2) was an important factor in the experimental HPS. However, the role of COX-2 in the directional collective migration of human pulmonary microvascular endothelial cells (HPMVECs) is unclear. Our study aims to evaluate the potential effect of COX-2 in the directional collective migration of HPMVECs under the stimulation of HPS patient serum. In this study, 9 patients with stable liver cirrhosis were screened for presence of HPS. We confirmed that HPS patient serum dramatically promoted the directional collective migration and angiogenesis of HPMVECs, while the COX-2 selective antagonist parecoxib significantly inhibited the directional collective migration of HPMVEC under the stimulation of HPS patient serum. In addition, HPS patient serum significantly upregulated the phosphorylation of PKC and promoted the activation of Rac via COX-2/PGE2 signaling pathway. Notably, silencing PKC activation attenuated the directional collective migration of HPMVEC induced by HPS patient serum. In conclusion, these results indicate that PKC/Rac signaling induced by COX-2 modulates collective directional migration of HPMVEC during pathological pulmonary angiogenesis in HPS patients.
['Tang|Xi|X|', 'Liu|Chang|C|', 'Chen|Lin|L|', 'Yang|Zhiyong|Z|', 'Belguise|Karine|K|', 'Wang|Xiaobo|X|', 'Lu|Kaizhi|K|', 'Yan|Hong|H|', 'Yi|Bin|B|']
D000328:Adult D016022:Case-Control Studies D002465:Cell Movement D002478:Cells, Cultured D051545:Cyclooxygenase 1 D015232:Dinoprostone D042783:Endothelial Cells D004730:Endothelium, Vascular D005260:Female D020065:Hepatopulmonary Syndrome D006801:Humans D008297:Male D008875:Middle Aged D009389:Neovascularization, Pathologic D010766:Phosphorylation D011493:Protein Kinase C D044967:Serum D015398:Signal Transduction D020744:rac GTP-Binding Proteins
Cyclooxygenase-2 Hepatopulmonary syndrome Angiogenesis Collective cell migration Pulmonary vascular endothelial cells