Open AccessTissue Inhibitor of Metalloproteinases-2 Mediates Kidney Injury during Sepsis
Author(s) -
Xiang Wen,
Jicheng Zhang,
Xiaojian Wan,
A. Frank,
Xin Qu,
John A. Kellum
Publication year - 2020
Publication title -
the nephron journals/nephron journals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.951
H-Index - 72
eISSN - 2235-3186
pISSN - 1660-8151
DOI - 10.1159/000511165
Subject(s) - medicine , acute kidney injury , sepsis , urinary system , kidney , histology , tissue inhibitor of metalloproteinase , matrix metalloproteinase , lumen (anatomy) , inflammation , nephrology , pathology
Urinary tissue inhibitor of metalloproteinases (TIMP)-2 has been identified as a predictive marker for acute kidney injury (AKI), including sepsis-associated AKI (S-AKI). Whether TIMP-2 might be causally related to AKI and hence represent a viable drug target is unclear. Objective: The aim of this study was to evaluate whether suppression of TIMP-2 attenuates S-AKI. Methods: Balb/c mice were randomized to sham or cecal ligation and puncture surgery and treated with or without a TIMP-2-neutralizing antibody. Animals were followed for 48 h and then sacrificed for analysis of TIMP-2 expression, cell cycle, and histology. Results: Anti-TIMP-2 resulted in decreased lumen TIMP-2 expression which markedly increased cell cycle progression and attenuated epithelial cell injury by histology. Conclusions: TIMP-2 mediates S-AKI and appears to be a viable drug target.