Amplified response of drug-induced liver fibrosis immune cell co-culture in a 3D hepatic fibrosis model.

Liver fibrosis, a critical consequence of chronic liver diseases, is characterized by excessive extracellular matrix (ECM) deposition driven by inflammation. This process involves complex interactions among hepatocytes, hepatic stellate cells (HSCs), and Kupffer cells, the liver's resident macrophages. Kupffer cells are essential in initiating fibrosis through the release of pro-inflammatory cytokines that activate HSCs.

In Vitro Nonalcoholic Fatty Liver Disease Model Elucidating the Effect of Immune Environment on Disease Progression and Alleviation.

Nonalcoholic fatty liver disease (NAFLD), which is a major cause of chronic liver disease, is characterized by fat accumulation in the liver. Existing models struggle to assess medication effects on liver function in the context of NAFLD's unique inflammatory environment. We address this by developing a 3D in vitro NAFLD model using HepG2 and THP-1 cells (mimicking liver and Kupffer cells) cocultured using transwell and hydrogel system.

Development of an In Vitro Model for Inflammation Mediated Renal Toxicity Using 3D Renal Tubules and Co-Cultured Human Immune Cells.

Background: The emergence of various infectious diseases and the toxic effects of hyperinflammation by biotherapeutics have highlighted the need for in vitro preclinical models mimicking the human immune system. In vitro models studying the relationship between hyperinflammation and acute renal injury mainly rely on 2D culture systems, which have shown limitations in recapitulating kidney function. Herein, we developed an in vitro kidney toxicity model by co-culturing 3D engineered kidney proximal tubules cells (RPTEC/TERT1) with human peripheral blood mononuclear cells (PBMC).

Structural basis for recognition and methylation of p97 by METTL21D, a valosin-containing protein lysine methyltransferase.

p97 is a human AAA+ (ATPase associated with diverse cellular activities, also known as valosin-containing protein [VCP]) ATPase, which is involved in diverse cellular processes such as membrane fusion and proteolysis. Lysine-specific methyltransferase of p97 (METTL21D) was identified as a class I methyltransferase that catalyzes the trimethylation of Lys315 of p97, a so-called VCP lysine methyltransferase (VCPKMT). Interestingly, VCPKMT disassembles a single hexamer ring consisting of p97-D1 domain and methylates Lys315 residue.