Glomerular Injury Is Exacerbated in Lupus-Prone MRL/lpr Mice Treated with a Protease-Activated Receptor 2 Antagonist.

Glomerular Injury Is Exacerbated in Lupus-Prone MRL/lpr Mice Treated with a Protease-Activated Receptor 2 Antagonist. Tohoku J Exp Med. 2019;249(2):127-133 Authors: Itto R, Oe Y, Imaruoka K, Sato E, Sekimoto A, Yamakage S, Kumakura S, Sato H, Ito S, Takahashi N Abstract Systemic lupus erythematosus (SLE) is characterized by the production of autoantibodies, which causes multi-organ injury such as lupus nephritis. SLE is associated with hypercoagulability. Activated coagulation factors such as tissue factor and VIIa complex and factor Xa activate protease-activated receptor 2 (PAR2). PAR2 promotes cytokine production through mitogen-activated protein kinase or nuclear factor kappa B signaling, and previous reports demonstrated that inhibition of PAR2 alleviated kidney injuries such as diabetic kidney disease and renal fibrosis in animal models. However, the involvement of PAR2 in the pathogenesis of SLE remains unclear. We therefore administered a selective PAR2 peptide antagonist, FSLLRY-NH2, to SLE-prone 4-month-old MRL-Faslpr mice for 4 weeks. Treatment with FSLLRY-NH2 caused the significant increases in the glomerular mesangial proliferation, glomerular deposition of both immunoglobulin G and complement factor C3d, and glomerular infiltration of Mac2-positive macrophages and CD3-positive T cells, compared with MRL-Faslpr mice treated with saline. In addition, the treatment with the PAR2 antagonist increased renal expression levels...
Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research