NLRP3 inflammasome mediates contrast media-induced acute kidney injury by regulating cell apoptosis.

Abstract

Iodinated contrast media serves as a direct causative factor of acute kidney injury (AKI) and is involved in the progression of cellular dysfunction and apoptosis. Emerging evidence indicates that NLRP3 inflammasome triggers inflammation, apoptosis and tissue injury during AKI. Nevertheless, the underlying renoprotection mechanism of NLRP3 inflammasome against contrast-induced AKI (CI-AKI) was still uncertain. This study investigated the role of NLRP3 inflammasome in CI-AKI both in vitro and in vivo. In HK-2 cells and unilateral nephrectomy model, NLRP3 and NLRP3 inflammasome member ASC were significantly augmented with the treatment of contrast media. Moreover, genetic disruption of NLRP3 notably reversed contrast-induced expression of apoptosis related proteins and secretion of proinflammatory factors, similarly to the effects of ASC deletion. Consistent with above results, absence of NLRP3 in mice undergoing unilateral nephrectomy also protected against contrast media-induced renal cells phenotypic alteration and cell apoptosis via modulating expression level of apoptotic proteins. Collectively, we demonstrated that NLRP3 inflammasome mediated CI-AKI through modulating the apoptotic pathway, which provided a potential therapeutic target for the treatment of contrast media induced acute kidney injury.

• Authors: Jianxiao Shen, Ling Wang, Na Jiang, Shan Mou, Minfang Zhang, Leyi Gu, Xinghua Shao, Qin Wang, Chaojun Qi, Shu Li, Wanpeng Wang, Xiajing Che, Zhaohui Ni
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 34682 (10 10 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27721494 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CARD Signaling Adaptor Proteins
• Contrast Media
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• PYCARD protein, human

Topics

• Acute Kidney Injury (chemically induced, genetics, metabolism)
• Animals
• Apoptosis
• CARD Signaling Adaptor Proteins (genetics, metabolism)
• Cell Line
• Contrast Media (adverse effects)
• Disease Models, Animal
• Humans
• Inflammasomes (metabolism)
• Mice
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Up-Regulation