2. Academic Validation
  3. Effects of a spleen tyrosine kinase inhibitor on progression of the lupus nephritis in mice

Effects of a spleen tyrosine kinase inhibitor on progression of the lupus nephritis in mice

  • J Pharmacol Sci. 2017 May;134(1):29-36. doi: 10.1016/j.jphs.2017.02.015.
Maki Kitai 1,  Noboru Fukuda 2,  Takahiro Ueno 1,  Morito Endo 3,  Takashi Maruyama 1,  Masanori Abe 1,  Kazuyoshi Okada 1,  Masayoshi Soma 4,  Koichi Matsumoto 1
Affiliations

Affiliations

  • 1 Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
  • 2 Division of Nephrology Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan; Research Center of Nihon University, Tokyo, Japan. Electronic address: [email protected].
  • 3 Faculty of Human Health Science, Hachinohe Gakuin University, Hachinohe, Aomori, Japan.
  • 4 Division of General Medicine, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
PMID: 28479222 DOI: 10.1016/j.jphs.2017.02.015
Abstract

The Fc Receptors (FcR) have pivotal roles in the pathogenesis of the autoimmune glomerulonephritis. We therefore investigated the effects of a Syk Inhibitor on the progression of lupus nephritis and SH3 domain binding protein 2 and p38MAP kinase signalings in mice. NZB/W F1 mice, a model of lupus nephritis, received a Syk Inhibitor R406. Western blotting and immunohistochemistry revealed that R406 treatment significantly delayed the appearance of proteinuria, histologically improved their glomerulosclerosis and inhibited the increased the expression of MCP-1 and TGF-β1 mRNAs and the nephrin and podocin proteins in the kidney. The treatment suppressed the phosphorylation of 3BP2 in white blood cells from the spleen and significantly inhibited the phosphorylation of p38MAPK in the kidney but did not affect expression of neonatal Fc receptor. These findings indicate the important roles and mechanisms of Fcγ receptors I and III in the development of autoimmune glomerulonephritis and suggest the possible application of Syk inhibitors as novel medicines for the glomerulonephritis.

Keywords

3BP2; Fc receptor; Lupus nephritis; Syk; p38MAP kinase.

Figures
Products