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CD147 promotes MTX resistance by immune cells through up-regulating ABCG2 expression and function.

Shuang Zhao1, Chen Chen, Shuang Liu

  • 1Department of Dermatology, XiangYa Hospital, Central South University, Changsha, Hunan, People's Republic of China.

Journal of Dermatological Science
|April 30, 2013
PubMed
Summary

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CD147 promotes methotrexate (MTX) resistance in psoriasis by increasing ABCG2 transporter activity, leading to reduced drug accumulation and apoptosis in immune cells. Targeting CD147 may overcome MTX resistance in psoriatic patients.

Area of Science:

  • Immunology
  • Dermatology
  • Pharmacology

Background:

  • Methotrexate (MTX) treats psoriasis by inducing immune cell apoptosis, but resistance is a clinical challenge.
  • CD147 is highly expressed in psoriatic PBMCs and implicated in MTX resistance, though mechanisms are unclear.

Purpose of the Study:

  • To elucidate the role of CD147 in mediating methotrexate resistance in immune cells.

Main Methods:

  • Assessed CD147 and ABCG2 expression, apoptosis, and intracellular MTX in psoriatic PBMCs.
  • Utilized CD147-overexpressing CHO cells and CD147-knockdown Jurkat T cells to evaluate drug sensitivity.
  • Investigated CD147-ABCG2 interaction via immunoprecipitation.

Main Results:

  • Psoriatic PBMCs showed higher CD147/ABCG2 expression and MTX resistance compared to healthy controls.

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  • CD147 overexpression in CHO cells increased ABCG2, reduced apoptosis, and lowered intracellular MTX.
  • CD147 knockdown in Jurkat T cells decreased ABCG2, enhanced MTX-induced apoptosis, and reduced MTX efflux.
  • The transmembrane domain of CD147 mediates interaction with ABCG2.

    • Conclusions:

    • CD147 regulates ABCG2-mediated MTX transport in immune cells, contributing to MTX resistance in psoriasis.
    • Targeting CD147 presents a potential therapeutic strategy for MTX-resistant psoriatic patients.