English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Nonalcoholic steatohepatitis (NASH) is an inflammatory form of nonalcoholic fatty liver disease that progresses to liver cirrhosis. It is still unknown how only limited patients with fatty liver develop NASH. Tumor necrosis factor (TNF)-α is one of the key molecules in initiating the vicious circle of inflammations. Nardilysin (N-arginine dibasic convertase; Nrd1), a zinc metalloendopeptidase of the M16 family, enhances ectodomain shedding of TNF-α, resulting in the activation of inflammatory responses. In this study, we aimed to examine the role of Nrd1 in the development of NASH.  Nrd1 +/+   and  Nrd1 −/−   mice were fed a control choline-supplemented amino acid-defined (CSAA) diet or a choline-deficient amino acid-defined (CDAA) diet. Fatty deposits were accumulated in the livers of both  Nrd1 +/+   and  Nrd1 −/−   mice by the administration of the CSAA or CDAA diets, although the amount of liver triglyceride in  Nrd1 −/−   mice was lower than that in  Nrd1 +/+   mice. Serum alanine aminotransferase levels were increased in  Nrd1 +/+   mice but not in  Nrd1 −/−   mice fed the CDAA diet. mRNA expression of inflammatory cytokines were decreased in  Nrd1 −/−   mice than in  Nrd1 +/+   mice fed the CDAA diet. While TNF-α protein was detected in both  Nrd1 +/+   and  Nrd1 −/−   mouse livers fed the CDAA diet, secretion of TNF-α in  Nrd1 −/−   mice was significantly less than that in  Nrd1 +/+   mice, indicating the decreased TNF-α shedding in  Nrd1 −/−   mouse liver. Notably, fibrotic changes of the liver, accompanied by the increase of fibrogenic markers, were observed in  Nrd1 +/+   mice but not in  Nrd1 −/−   mice fed the CDAA diet. Similar to the CDAA diet, fibrotic changes were not observed in  Nrd1 −/−   mice fed a high-fat diet. Thus, deletion of nardilysin prevents the development of diet-induced steatohepatitis and liver fibrogenesis. Nardilysin could be an attractive target for anti-inflammatory therapy against NASH.

Deletion of Nardilysin Prevents the Development of Steatohepatitis and Liver Fibrotic Changes