Deficiency of cold-inducible ribonucleic acid-binding protein reduces renal injury after ischemia-reperfusion

• Published in: Surgery 2016-08, Vol.160 (2), p.473-483
• Main Authors: Cen, Cindy, MD, Yang, Weng-Lang, PhD, Yen, Hao-Ting, MS, Nicastro, Jeffrey M., MD, Coppa, Gene F., MD, Wang, Ping, MD
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - etiology; Acute Kidney Injury - metabolism; Acute Kidney Injury - prevention & control; Animals; Blood Urea Nitrogen; Creatinine - metabolism; Disease Models, Animal; Interleukin-6 - metabolism; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Reperfusion Injury - etiology; Reperfusion Injury - metabolism; Reperfusion Injury - prevention & control; RNA-Binding Proteins - physiology; Surgery
• ISSN: 0039-6060; 1532-7361
• DOI: 10.1016/j.surg.2016.04.014

Background Renal ischemia-reperfusion injury, commonly caused by major operation and shock, leads to acute kidney injury and is associated with high morbidity and mortality. Cold-inducible ribonucleic acid-binding protein, a cold shock protein, has recently been identified as a damage-associated molecular pattern. We hypothesized that cold-inducible ribonucleic acid-binding protein exacerbates severity of injury in renal ischemia-reperfusion. Methods Renal ischemia was induced in an 8-week-old male C57BL/6 wild-type mice and Cirp−/− mice via bilateral clamping of renal pedicles for 30 minutes, followed by reperfusion for 5 or 24 hours and harvest of blood and renal tissue for analysis. Anti–cold-inducible ribonucleic acid-binding protein antibody or non-immunized immunoglobulin G (IgG) was injected intravenously (10 mg/kg body weight) at time of reperfusion. Results After renal ischemia-reperfusion, Cirp−/− mice demonstrated a reduction of blood urea nitrogen and creatinine of 53% and 60%, respectively, compared with wild-type mice. Serum IL-6 levels were reduced significantly: 70% in Cirp−/− mice compared with wild-type mice after renal ischemia-reperfusion. Levels of nitrotyrosine, an oxidatively modified protein marker, and cyclooxygenase-2, an inflammatory mediator, also were significantly decreased in the kidneys of the Cirp−/− mice compared with wild-type mice after renal ischemia-reperfusion. Renal caspase-3 activity was decreased in Cirp−/− mice compared with wild-type mice after renal ischemia-reperfusion, which corresponded to the reduction of apoptotic cells determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Injection of neutralizing anti-cold-inducible ribonucleic acid-binding protein antibody into wild-type mice led to an 82% reduction in blood urea nitrogen compared with the vehicle after renal ischemia-reperfusion. Conclusion Deficiency of cold-inducible ribonucleic acid-binding protein results in less renal injury after renal ischemia-reperfusion by attenuating inflammation and oxidative stress. Furthermore, blockade of cold-inducible ribonucleic acid-binding protein shows a protective effect, indicating cold-inducible ribonucleic acid-binding protein as a target in the treatment of renal ischemia-reperfusion.