title: Targeting spleen tyrosine kinase-Bruton's tyrosine kinase axis for immunologically mediated glomerulonephritis.
abstract: The importance of B-cell activation and immune complex-mediated Fc-receptor activation in the pathogenesis of immunologically mediated glomerulonephritis has long been recognized. The two nonreceptor tyrosine kinases, spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (Btk), are primarily expressed by hematopoietic cells, and participate in B-cell-receptor- and Fc-receptor-mediated activation. Pharmacological inhibitors of Syk or Btk are undergoing preclinical development and clinical trials for several immune diseases; and Syk inhibitors have been shown to reduce disease activity in rheumatoid arthritis patients. However, the clinical therapeutic efficacies of these inhibitors in glomerulonephritis have not been evaluated. Herein, we review recent studies of Syk and Btk inhibitors in several experimental primary and secondary glomerulonephritis models. These inhibitors suppressed development of glomerular injury, and also ameliorated established kidney disease. Thus, targeting Syk and Btk signaling pathways is a potential therapeutic strategy for glomerulonephritis, and further evaluation is recommended.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Tri-Service General Hospital, Taipei 114, Taiwan.
authors.forename: Jin-Shuen
authors.initials: JS
authors.lastname: Chen
authors.affiliation: School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Li-Chien
authors.initials: LC
authors.lastname: Chang
authors.affiliation: School of Pharmacy, College of Pharmacy, China Medical University, Taichung 404, Taiwan ; Chinese Medicine Research and Development Center, and Center for Molecular Medicine, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Shyh-Jer
authors.initials: SJ
authors.lastname: Huang
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan ; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: Chao-Wen
authors.identifier: 0000-0002-0466-6630
authors.initials: CW
authors.lastname: Cheng
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D005921:Glomerulonephritis / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D000072377:Syk Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse