title: CD147 promotes MTX resistance by immune cells through up-regulating ABCG2 expression and function.
abstract: BACKGROUND
  Methotrexate (MTX) is a drug used to treat psoriasis due to inducing immune cell apoptosis. However, certain patients show MTX resistant. CD147, highly expressed by psoriatic PBMCs, is assumed to regulate MTX sensitivity. The underlining mechanism is still relatively understudied.
  
  
  OBJECTIVE
  To understand the mechanisms of that CD147 promotes MTX resistance in immune cells.
  
  
  METHODS
  The expression of CD147 and ABCG2 in PBMCs from psoriatic patients, cellular apoptosis and intracellular MTX amount were measured. We also checked the cellular drug sensitivity of CHO (Chinese Hamster Ovary) cell lines with introduced CD147 and Jurkat T cells depeleted CD147. By immunoprecipitation, we detected the interaction between CD147 and ABCG2.
  
  
  RESULTS
  Both ABCG2 and CD147 are highly expressed in psoriatic PBMCs. Cultured in vitro, the PBMCs from psoriatic patients were more resistant to MTX-induced apoptosis comparing to PBMCs from healthy people. Further studies demonstrated that exogenous overexpression of CD147 in CHO cells increased ABCG2 protein level. After MTX treatment, CD147 overexpressing CHO cells showed lower apoptosis rate and lower intracellular MTX concentration. On the contrary, knockdown of CD147 by shRNA in Jurkat T cells decreased ABCG2 expression, as well as increased MTX-induced apoptosis and decreased MTX efflux. Immunoprecipitation experiment revealed that the trans-membrane domain of CD147 conferred its' interaction with ABCG2.
  
  
  CONCLUSIONS
  Our study suggests a role of CD147 in regulating ABCG2 transportation of MTX in immune cells. Strategies involving targeting CD147 could be considered in clinical treatment of psoriatic patients resistant to MTX.
authors.affiliation: Department of Dermatology, XiangYa Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.forename: Weiqi
authors.initials: W
authors.lastname: Zeng
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.forename: Lisha
authors.initials: L
authors.lastname: Wu
authors.forename: Zhongling
authors.initials: Z
authors.lastname: Luo
authors.forename: Shuangyuan
authors.initials: S
authors.lastname: Zhou
authors.forename: Qingling
authors.initials: Q
authors.lastname: Li
authors.forename: Jianglin
authors.initials: J
authors.lastname: Zhang
authors.forename: Yehong
authors.initials: Y
authors.lastname: Kuang
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051926:Basigin / Q000378:metabolism*; D016466:CHO Cells; D016022:Case-Control Studies; D002648:Child; D006224:Cricetinae; D003412:Cricetulus; D003879:Dermatologic Agents / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000378:metabolism / Q000494:pharmacology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D034622:RNA Interference; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C497886:BSG protein, human; D003879:Dermatologic Agents; D009363:Neoplasm Proteins; D051926:Basigin; D008727:Methotrexate