In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 10 ( 2023-10-20), p. e0291880-
Abstract:
Lipopolysaccharide (LPS) derived from Porphyromonas gingivalis ( P . g .), which causes periodontal disease, contributes to the development of non-alcoholic steatohepatitis (NASH). We investigated the role of Nrf2, an antioxidative stress sensor, in macrophages in the development of NASH induced by LPS from P . g . We generated macrophage-specific Nrf2 gene rescue mice ( Nrf2 -mRes), which express Nrf2 only in macrophages, using the cre/loxp system. Wild-type (WT) mice, whole body Nrf2 -knockout ( Nrf2 -KO) mice, and Nrf2 -mRes mice were fed a high-fat diet for 18 weeks, and LPS from P . g . was administered intraperitoneally for the last 6 weeks. Nrf2 -KO mice developed severe steatohepatitis with liver inflammation and fibrosis compared with WT mice, and steatohepatitis was ameliorated in Nrf2 -mRes mice. The mRNA expressions of Toll-like receptor ( Tlr ) -2 , which activates inflammatory signaling pathways after LPS binding, and α-smooth muscle actin ( αSma ), which promotes hepatic fibrosis, were reduced in Nrf2 -mRes mice compared with Nrf2 -KO mice. The protein levels of LPS-binding protein in livers were increased in Nrf2 -KO mice compared with WT mice; however, the levels were reduced in Nrf2 -mRes mice despite similar numbers of F4/80 positive cells, which reflect macrophage/Kupffer cell infiltration into the livers. Nrf2 in macrophages ameliorates NASH through the increased hepatic clearance of LPS.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0291880
DOI:
10.1371/journal.pone.0291880.g001
DOI:
10.1371/journal.pone.0291880.g002
DOI:
10.1371/journal.pone.0291880.g003
DOI:
10.1371/journal.pone.0291880.g004
DOI:
10.1371/journal.pone.0291880.g005
DOI:
10.1371/journal.pone.0291880.t001
DOI:
10.1371/journal.pone.0291880.s001
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2267670-3
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