Coagulation Factor Xa and Protease-Activated Receptor 2 as Novel Therapeutic Targets for Diabetic Nephropathy

Yuji Oe, Sakiko Hayashi, Tomofumi Fushima, Emiko Sato, Kiyomi Kisu, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi

研究成果: Article査読

45 被引用数 (Scopus)

抄録

Objective - The role of hypercoagulability in the pathogenesis of diabetic nephropathy (DN) remains elusive. We recently reported the increased infiltration of macrophages expressing tissue factor in diabetic kidney glomeruli; tissue factor activates coagulation factor X (FX) to FXa, which in turn stimulates protease-activated receptor 2 (PAR2) and causes inflammation. Approach and Results - Here, we demonstrated that diabetes mellitus increased renal FX mRNA, urinary FXa activity, and FX expression in glomerular macrophages. Administration of an oral FXa inhibitor, edoxaban, ameliorated DN with concomitant reductions in the expression of PARs (Par1 and Par2) and of proinflammatory and profibrotic genes. Diabetes mellitus induced PAR2, and lack of Par2 ameliorated DN. FXa or PAR2 agonist increased inflammatory cytokines in endothelial cells and podocytes in vitro. Conclusions - We conclude that enhanced FXa and PAR2 exacerbate DN and that both are promising targets for preventing DN. Alleviating inflammation is probably more important than inhibiting coagulation per se when treating kidney diseases using anticoagulants.

本文言語English
ページ(範囲)1525-1533
ページ数9
ジャーナルArteriosclerosis, thrombosis, and vascular biology
36
8
DOI
出版ステータスPublished - 2016 8 1

ASJC Scopus subject areas

  • 循環器および心血管医学

フィンガープリント

「Coagulation Factor Xa and Protease-Activated Receptor 2 as Novel Therapeutic Targets for Diabetic Nephropathy」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル