The level of CD147 expression correlates with cyclophilin-induced signalling and chemotaxis

Abstract

BackgroundPrevious studies identified CD147 as the chemotactic receptor on inflammatory leukocytes for extracellular cyclophilins (eCyp). However, CD147 is not known to associate with signal transducing molecules, so other transmembrane proteins, such as proteoglycans, integrins, and CD98, were suggested as receptor or co-receptor for eCyp. CD147 is ubiquitously expressed on many cell types, but relationship between the level of CD147 expression and cellular responses to eCyp has never been analyzed. Given the role of eCyp in pathogenesis of many diseases, it is important to know whether cellular responses to eCyp are regulated at the level of CD147 expression.ResultsHere, we manipulated CD147 expression levels on HeLa cells using RNAi and investigated the signalling and chemotactic responses to eCypA. Both Erk activation and chemotaxis correlated with the level of CD147 expression, with cells exhibiting low level expression being practically unresponsive to eCypA.ConclusionsOur results provide the first demonstration of a chemotactic response of HeLa cells to eCypA, establish a correlation between the level of CD147 expression and the magnitude of cellular responses to eCypA, and indicate that CD147 may be a limiting factor in the receptor complex determining cyclophilin-induced Erk activation and cell migration.

CD147 and CD98 complex-mediated homotypic aggregation attenuates the CypA-induced chemotactic effect on Jurkat T cells

“…The cyclophilin-CD147 interaction has been reported to participate in the development and/or progression of many types of inflammatory responses (Yurchenko et al, 2006). Previous studies reported that CypA-induced chemotactic activity was increased in activated T cells following with the up-regulation of CD147 (Trachtenberg et al, 2011). Our previous study also showed that CD147 was up-regulated in monocytes/macrophages, and enhanced CypA-mediated cell migration was observed in the case of rheumatoid arthritis (Zhu et al, 2005).…”

Regulation of EMMPRIN (CD147) on monocyte subsets in patients with symptomatic coronary artery disease

“…EMMPRIN expression levels correlate with its biological function [10]. Based on these facts, our findings indicate that upregulation of EMMPRIN on classical monocytes could be the leading cause for plaque rupture.…”

Secreted cyclophilin A mediates G1/S phase transition of cholangiocarcinoma cells via CD147/ERK1/2 pathway

“…Specific inhibitors against CypA such as cyclosporin A (CsA) or against CypA/CD147 binding (Licartin) may effectively inhibit CCA cell proliferation and tumor progression. Dotted lines represent molecular events demonstrated in the present study CD147 expression levels, CD147 is considered as a ratelimiting factor in the receptor complex responding to sCypA [34]. Anti-CD147 monoclonal antibody has already been used for preventing invasion and metastasis of human cancer, e.g., head and neck carcinoma [51][52][53].…”

“…Since CypA is shown to regulate the expression of CD147 [34][35][36], we further elucidated whether alteration of CypA expression affects CD147 expression level. Real-time PCR and Western blot of CD147 were determined in siCypA-treated and the SC cells of three CCA cell lines.…”