Macrophage-derived Osteopontin (SPP1) Protects From Nonalcoholic Steatohepatitis.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning degeneration, and fibrosis, all of which increase the risk of progression to end-stage liver disease. Osteopontin (OPN, SPP1) plays an important role in macrophage (MF) biology, but whether MF-derived OPN affects NASH progression is unknown.

Methods: We analyzed publicly available transcriptomic datasets from patients with NASH, and used mice with conditional overexpression or ablation of Spp1 in myeloid cells and liver MFs, and fed them a high-fat, fructose, and cholesterol diet mimicking the Western diet, to induce NASH.

The Integrated "Multiomics" Landscape at Peak Injury and Resolution From Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (ALD) is a significant clinical problem for which the most effective therapy is alcohol abstinence. The two aims of this study were, first, to identify the liver transcriptome, fecal microbiome, and portal serum metabolome at peak injury and during early and late resolution from ALD; and second, to integrate their interactions and understand better the pathogenesis of ALD. To provoke alcohol-induced liver injury, female and male wild-type mice were fed the control or ethanol Lieber-DeCarli diets for 6 weeks.

Ablation of in Intestinal Epithelial Cells Causes Intestinal Lipid Accumulation and Reduces NASH in Mice.

Nonalcoholic steatohepatitis (NASH) is a metabolic disorder in which poor nutrition and the gut-to-liver interaction play a major role. We previously established that hepatic high mobility group box-1 (HMGB1) is involved in chronic liver disease. HMGB1 increases in patients with NASH and it is expressed in intestinal epithelial cells (IEC); yet, the role of intestinal HMGB1 in the pathogenesis of NASH has not been investigated.

High-Mobility Group Box-1 and Liver Disease.

High-mobility group box-1 (HMGB1) is a ubiquitous protein. While initially thought to be simply an architectural protein due to its DNA-binding ability, evidence from the last decade suggests that HMGB1 is a key protein participating in the pathogenesis of acute liver injury and chronic liver disease. When it is passively released or actively secreted after injury, HMGB1 acts as a damage-associated molecular pattern that communicates injury and inflammation to neighboring cells by the receptor for advanced glycation end products or toll-like receptor 4, among others.

Osteopontin deletion drives hematopoietic stem cell mobilization to the liver and increases hepatic iron contributing to alcoholic liver disease.

The aim of this study was to investigate the role of osteopontin (OPN) in hematopoietic stem cell (HPSC) mobilization to the liver and its contribution to alcoholic liver disease (ALD). We analyzed young (14-16 weeks) and old (>1.5 years) wild-type (WT) littermates and global knockout ( ) mice for HPSC mobilization to the liver.

Characterization of a functional C3A liver spheroid model.

More predictive liver models are a critical requirement for preclinical screening of compounds demonstrating hepatotoxic liability. 3D liver spheroids have been shown to have an enhanced functional lifespan compared to 2D monocultures; however a detailed characterisation of spatiotemporal function and structure of spheroids still needs further attention before widespread use in industry. We have developed and characterized the structure and function of a 3D liver spheroid model formed from C3A hepatoma cells.