Protease–activated receptor 2 exacerbates adenine–induced renal tubulointerstitial injury in mice

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

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Hypercoagulability is associated with chronic kidney disease (CKD). Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade are known to activate protease–activated receptor 2 (PAR2), and to cause inflammation and tissue injury. Although PAR2 is highly expressed in the kidney, it is unclear whether PAR2 plays a pathogenic role in CKD. To test this, we fed the mice lacking Par2 (F2rl1−/−) and wild type (F2rl1+/+) mice with adenine diet to induce tubulointerstitial injury, a hallmark of CKD. Adenine-treated mice showed severe renal dysfunction, tubular atrophy, and fibrosis. Fibrin deposition and the expression of tissue factor and PARs markedly increased in their kidneys. Lack of Par2 attenuated renal histological damage and reduced the expression levels of genes related to inflammation, fibrosis, and oxidative stress. Our data indicate that PAR2 is critically important in the pathogenesis of adenine-induced tubular injury. PAR2 antagonists under development could be useful to treat and prevent CKD.

Original languageEnglish
Pages (from-to)547-552
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2017 Jan 29


  • Coagulation factors
  • Fibrosis
  • Inflammation
  • Oxidative stress
  • Renal insufficiency


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