Role of CXCR4 in changes of protein C system in ulcerative colitis mice / 中国病理生理杂志

ABSTRACT

[ ABSTRACT] AIM: To explore the role of chemokine receptor CXCR 4 in the pathogenesis of protein C system (PCS) in ulcerative colitis (UC).METHODS:In vivo, the mice were divided into control group and UC group .The mac-roscopic score, microscopic score and ulcer index were assessed .The mRNA levels and activity of myeloperoxidase ( MPO) , cyclooxygenase-2 ( COX-2 ) , stromal cell-derived factor-1α( SDF-1α) and monocyte chemotactic protein 1 (MCP-1) both in colonic tissue and plasma were determined .The expression and location of CXCR4,β-arrestin, p-JNK, endothelial cell protein C receptor (EPCR) and thrombomodulin (TM) were detected.The activity of protein C (PC) and protein S ( PS) was measured in each group .In vitro, mouse colonic microvascular endothelial cells were isolated , cultured and identified.Both CXCR4-overexpressing and CXCR4-silencing colonic mucosa microvascular endothelial cells were con-structed.The effects of SDF-1αon the protein levels of EPCR , TM,β-arrestin and p-JNK, and on the activity of PC , PS and activated protein C ( APC) were observed .RESULTS:Compared with control group , UC mice showed increased gross score, histopathological score and ulcer index (P<0.05).The mRNA levels and activity of MPO, COX-2, SDF-1αand MCP-1 in colon and plasma were increased (P<0.01).The protein levels of CXCR4,β-arrestin and p-JNK were up-regu-lated, EPCR expression was down-regulated in colon, and the activity of PC and PS in plasma was decreased (P<0.05 or P<0.01).CXCR4 overexpression further aggravated SDF-1α-induced PCS inhibition in colonic mucosa microvascular en-dothelial cells, and further up-regulated the protein levels of β-arrestin and p-JNK (P<0.05).CONCLUSION:PCS is inhibited in UC.CXCR4 is involved in the regulation of PCS inhibition by mediating chemokines and acting on colonic mu -cosa microvascular endothelial cells through β-arrestin-JNK pathway .