LPS-TLR4 Pathway Mediates Ductular Cell Expansion in Alcoholic Hepatitis.

Title

LPS-TLR4 Pathway Mediates Ductular Cell Expansion in Alcoholic Hepatitis.

Creator

Odena Gemma; Chen Jiegen; Lozano Juan Jose; Altamirano Jose; Rodrigo-Torres Daniel; Affo Silvia; Morales-Ibanez Oriol; Matsushita Hiroshi; Zou Jian; Dumitru Raluca; Caballeria Juan; Gines Pere; Arroyo Vicente; You Min; Rautou Pierre-Emmanuel; Valla Dominique; Crews Fulton; Seki Ekihiro; Sancho-Bru Pau; Bataller Ramon

Publisher

Scientific reports

Date

2016
2016-10

Description

Alcoholic hepatitis (AH) is the most severe form of alcoholic liver disease for which there are no effective therapies. Patients with AH show impaired hepatocyte proliferation, expansion of inefficient ductular cells and high lipopolysaccharide (LPS) levels. It is unknown whether LPS mediates ductular cell expansion. We performed transcriptome studies and identified keratin 23 (KRT23) as a new ductular cell marker. KRT23 expression correlated with mortality and LPS serum levels. LPS-TLR4 pathway role in ductular cell expansion was assessed in human and mouse progenitor cells, liver slices and liver injured TLR4 KO mice. In AH patients, ductular cell expansion correlated with portal hypertension and collagen expression. Functional studies in ductular cells showed that KRT23 regulates collagen expression. These results support a role for LPS-TLR4 pathway in promoting ductular reaction in AH. Maneuvers aimed at decreasing LPS serum levels in AH patients could have beneficial effects by preventing ductular reaction development.

Subject

Alcoholic/*immunology; Animals; Cell Proliferation; Cells; Collagen/genetics/metabolism; Common/*pathology; Cultured; Female; Gene Expression Profiling; Gene Expression Regulation; Hepatic Duct; Hepatitis; Hepatocytes/*metabolism/pathology; Humans; Inbred BALB C; Keratins; Knockout; Lipopolysaccharides/metabolism; Male; Mice; Middle Aged; Signal Transduction; Toll-Like Receptor 4/genetics/*metabolism; Type I/genetics/*metabolism

Identifier

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

35610–35610

Volume

6

Citation

Odena Gemma; Chen Jiegen; Lozano Juan Jose; Altamirano Jose; Rodrigo-Torres Daniel; Affo Silvia; Morales-Ibanez Oriol; Matsushita Hiroshi; Zou Jian; Dumitru Raluca; Caballeria Juan; Gines Pere; Arroyo Vicente; You Min; Rautou Pierre-Emmanuel; Valla Dominique; Crews Fulton; Seki Ekihiro; Sancho-Bru Pau; Bataller Ramon, “LPS-TLR4 Pathway Mediates Ductular Cell Expansion in Alcoholic Hepatitis.,” NEOMED Bibliography Database, accessed June 21, 2021, https://neomed.omeka.net/items/show/4008.

Social Bookmarking