Journal Article

Protease-Activated Receptor 1 Contributes to Microcirculation Failure and Tubular Damage in Renal Ischemia-Reperfusion Injury in Mice

Nakano, Daisuke, Nishiyama, Akira, Tian, Ye, Zheng, Haofeng, Li, Lei, Zhang, Lei, Guan, Yu

2021

Overview

Ischemia-reperfusion- (IR-) induced kidney injury is difficult to avoid during renal transplantation and robot-assisted partial nephrectomy. Renal IR injury is characterized by tubular damage, microcirculation failure, and inflammation, which coordinately augment renal injury; however, no specific treatment is available for these conditions. Protease-activated receptor-1 (PAR-1) and its ligand, thrombin, are involved in coagulation and were shown to be associated with epithelial cell injury. Here, we hypothesized that PAR-1 exaggerated renal IR-induced tubular cell damage and microcirculation failure and that pharmacological inhibition of PAR-1 by Q94 could prevent these injuries. Renal warm IR increased the expression of PAR-1 in the renal tubules. Q94 attenuated renal IR-induced changes and histopathological damage. Microcirculation failure analyzed by congestion in the histopathology and blood cell flow examined by intravital multiphoton microscopy were suppressed by Q94 treatment. Q94 also dramatically increased tubular cell proliferation despite the lower renal damage. Thrombin suppressed cell proliferation and induced apoptosis in the tubules; these effects were prevented by Q94 treatment. Taken together, PAR-1 was associated with renal IR injury. Inhibition of PAR-1 ameliorated injury possibly by improving renal microcirculation and tubular cell survival/proliferation.

• Publisher: Hindawi,John Wiley & Sons, Inc
• Subject: Analysis / Animals / Antibodies / Apoptosis / Blood cells / Care and treatment / Cell growth / Cell injury / Cell proliferation / Cell survival / Coagulation / Creatinine / Damage / Diagnosis / Epithelial cells / Failure analysis / G proteins / Hemorrhage / Histochemistry / Histology / Histopathology / Identification and classification / Injury prevention / Ischemia / Kidney Diseases - drug therapy / Kidney Diseases - metabolism / Kidney Diseases - pathology / Kidney transplantation / Kidney Tubules - blood supply / Kidney Tubules - metabolism / Kidney Tubules - pathology / Kidneys / Laser scanning microscopy / Male / Methods / Mice / Microcirculation / Nephrectomy / Patient outcomes / Properties / Protease / Proteinase-activated receptor 1 / Receptor, PAR-1 - agonists / Receptor, PAR-1 - metabolism / Receptors / Renal tubules / Reperfusion / Reperfusion injury / Reperfusion Injury - drug therapy / Reperfusion Injury - metabolism / Reperfusion Injury - pathology / Risk factors / Robots / Surgery / Thrombin / Transplantation