Blocking junctional adhesion molecule c promotes the recovery of cisplatin-induced acute kidney injury

Sun Chul Kim, Yoon Sook Ko, Hee Young Lee, Myung-Gyu Kim, Sang Kyung Jo, Won Yong Cho

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background/Aims: Recent findings have demonstrated the occurrence of neutrophil transendothelial migration in the reverse direction (reverse TEM) and that endothelial junctional adhesion molecule C (JAM-C) is a negative regulator of reverse TEM. In this study, we tested the effects of a JAM-C blocking antibody on the resolution of kidney injuries and inflammation in a mouse model of cisplatin-induced acute kidney injury (AKI). Methods: Cisplatin was administered via intraperitoneal injection. A JAM-C blocking antibody or a control immunoglobulin G was administered intraperitoneal at 1.5 mg/kg, with the injection being delayed until day 4 following cisplatin administration to restrict the effect of antibodies on recovery. Results: After cisplatin injection, serum creatinine and histologic injuries peaked on day 4. Treatment with a JAM-C blocking antibody on days 4 and 5 promoted the functional and histologic recovery of cisplatin-induced AKI on days 5 and 6. Facilitating recovery with a JAM-C blocking antibody correlated with significantly increased circulating intercellular adhesion molecule 1+ Tamm-Horsfall protein+ neutrophils and significantly decreased renal neutrophil infiltration, indicating that facilitating reverse the TEM of neutrophils from the kidney to the peripheral circulation partially mediated the resolution of inflammation and recovery. Conclusions: These results demonstrated that reverse TEM is involved in the resolution of neutrophilic inflammation in cisplatin-induced AKI and that JAM-C is an important regulator of this process.

Original languageEnglish
Pages (from-to)1053-1061
Number of pages9
JournalKorean Journal of Internal Medicine
Volume32
Issue number6
DOIs
Publication statusPublished - 2017 Nov 1

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Keywords

  • Acute kidney injury
  • Cisplatin
  • Junctional adhesion molecule c
  • Transendothelial and transepithelial migration

ASJC Scopus subject areas

  • Internal Medicine

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