Involvement of the NLRC4-inflammasome in diabetic nephropathy

Fang Yuan, Ryan Kolb, Gaurav Pandey, Wei Li, Lin Sun, Fuyou Liu, Fayyaz S. Sutterwala, Yinghong Liu, Weizhou Zhang

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. The role of inflammation in DN has only recently been recognized. It has been shown that the NLRP3-inflammasome contributes to DN development by inducing interleukin (IL)-1β processing and secretion. In an effort to understand other IL-1β activating mechanism during DN development, we examined the role of the NLRC4-inflammasome in DN and found that NLRC4 is a parallel mechanism, in addition to the NLRP3-inflammasome, to induce pro-IL-1β processing and activation. We found that the expression of NLRC4 is elevated in DN kidneys. NLRC4-deficiency results in diminished DN disease progression, as manifested by a decrease in blood glucose and albumin excretion, as well as preserved renal histology. We further found that DN kidneys have increased F4/80+ macrophages, increased IL-1β production, and other signaling pathways related to kidney pathology such as activation of NF-κB and MAP kinase pathways, all of which were rescued by NLRC4-deficiency. This study demonstrates NLRC4-driven IL-1β production as critical for the progression of DN, which underscores the importance to target this pathway to alleviate this devastating disease.

Original languageEnglish
Article numbere0164135
JournalPLoS ONE
Volume11
Issue number10
DOIs
StatePublished - Oct 2016
Externally publishedYes

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