Odontogenic infection by Porphyromonas gingivalis exacerbates fibrosis in NASH via hepatic stellate cell activation.

Scientific Reports
Atsuhiro NagasakiMutsumi Miyauchi

Abstract

Odontogenic infection of Porphyromonas gingivalis (P.g.), a major periodontal pathogen, exacerbates pathological progression of non-alcoholic steatohepatitis (NASH). In this study, we aimed to clarify the detailed mechanism in which P.g. induced hepatic stellate cells (HSCs; key effector cells in liver fibrosis) activation. In the liver of high fat diet-induced NASH mouse model with P.g. odontogenic infection, immunolocalization of P.g. was detected. The number of hepatic crown-like structure, which was macrophage aggregation and related to liver fibrosis, was drastically increased and fibrosis area was also increased through upregulating immunoexpression of Phosphorylated Smad2 (key signaling molecule of TGF-β1) and Galectin-3. P.g.-secreted trypsin-like enzyme [gingipain; an activator of protease-activated receptor 2 (PAR2)] stimulated HSC proliferation and differentiation through Smad and ERK signaling induced by TGF-β1 produced from HSCs with P.g.-infection. Further, Galectin-3 produced from HSCs with P.g. infection and P.g.-derived LPS/lipoprotein stimulation stabilized TGFβ-receptor II resulting in increasing sensitivity for TGF-β1, finally leading to HSC differentiation via activating Smad and ERK signaling. In addition ...Continue Reading

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Citations

Jan 30, 2021·Nature Reviews. Immunology·George Hajishengallis, Triantafyllos Chavakis
Feb 17, 2021·Journal of Cardiovascular Electrophysiology·Shunsuke MiyauchiYukiko Nakano
Apr 4, 2021·International Journal of Environmental Research and Public Health·Fumihiko UchidaJunichi Shoda
May 1, 2021·Cancers·Se-Young ParkNa-Young Song
May 1, 2021·International Journal of Molecular Sciences·Masahiro HatasaSayaka Katagiri
Jul 13, 2021·Journal of Clinical Periodontology·Atsuhiro NagasakiMutsumi Miyauchi

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