TargetRx Atlas

MRNA basic information

  • mRNA ID:ENST00000224784
  • Gene Name:ACTA2
  • mRNA database:Ensembl
  • mRNA expression :down-regulated
  • mRNA Method:PCR
  • mRNA Pathway:NA
  • Evidence:validated
  • (mRNA-drug)

Drug basic information

  • Drug ID:DB09053
  • Drug Name:Ibrutinib
  • Drug Method:down-regulated the gene expression

Disease basic infommation

  • Disease:endometriosis
  • Tissue:tissue

Other information

  • Title:B lymphocytes inactivation by Ibrutinib limits endometriosis progression in mice
  • Journal:Human Reproduction
  • Published:2019
  • PubMed ID:31247078
  • Abstract:Summary answer:Skewing activated B cells toward regulatory B cells (Bregs) by Bruton＇s tyrosine kinase (Btk) inhibition using Ibrutinib prevents endometriosis progression in mice while B cell depletion using an anti-CD20 antibody has no effect. What is known already:A polyclonal activation of B cells and the presence of anti-endometrial autoantibodies have been described in a large proportion of women with endometriosis though their exact role in the disease mechanisms remains unclear. Study design, size, duration:This study included comparison of endometriosis progression for 21 days in control mice versus animals treated with the anti-CD20 depleting antibody or with the Btk inhibitor Ibrutinib that prevents B cell activation. Participants/materials, setting, methods:After syngeneic endometrial transplantation, murine endometriotic lesions were compared between treated and control mice using volume, weight, ultrasonography, histology and target genes expression in lesions. Phenotyping of activated and regulatory B cells, T lymphocytes and macrophages was performed by flow cytometry on isolated spleen and peritoneal cells. Cytokines were assayed by ELISA. Main results and the role of chance:Btk inhibitor Ibrutinib prevented lesion growth, reduced mRNA expression of cyclooxygenase-2, alpha smooth muscle actin and type I collagen in the lesions and skewed activated B cells toward Bregs in the spleen and peritoneal cavity of mice with endometriosis. In addition, the number of M2 macrophages decreased in the peritoneal cavity of Ibrutinib-treated mice compared to anti-CD20 and control mice. Depletion of B cells using an anti-CD20 antibody had no effect on activity and growth of endometriotic lesions and neither on the macrophages, compared to control mice.
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