Related Experiment Video
Updated: Sep 4, 2025
Isolation and Characterization of Mouse Primary Liver Sinusoidal Endothelial Cells
Published on: December 16, 2021
Carma3 Protects from Liver Injury by Preserving Mitochondrial Integrity in Liver Sinusoidal Endothelial Cells
Liqing Cheng1,2, Zhanqi Wei1, Zaopeng Yang1
1Department of Basic Medical Sciences, Tsinghua University School of Medicine, Beijing, China.
Abstract:
Carma3 is an intracellular scaffolding protein that can form complex with Bcl10 and Malt1 to mediate G protein-coupled receptor- or growth factor receptor-induced NF-κB activation. However, the in vivo function of Carma3 has remained elusive. Here, by establishing a Con A-induced autoimmune hepatitis model, we show that liver injury is exacerbated in Carma3 -/- mice. Surprisingly, we find that the Carma3 expression level is higher in liver sinusoidal endothelial cells (LSECs) than in hepatocytes in the liver. In Carma3 -/- mice, Con A treatment induces more LSEC damage, accompanied by severer coagulation. In vitro we find that Carma3 localizes at mitochondria and Con A treatment can trigger more mitochondrial damage and cell death in Carma3-deficient LSECs. Taken together, our data uncover an unrecognized role of Carma3 in maintaining LSEC integrity, and these results may extend novel strategies to prevent liver injury from toxic insults.
Insights
Carma3 protein deficiency worsens liver injury in mice. Carma3 loss in liver sinusoidal endothelial cells (LSECs) increases damage and coagulation, highlighting its role in LSEC integrity.
Area of Science:
- Immunology
- Cell Biology
- Hepatology
Background:
- Carma3 is an intracellular scaffolding protein involved in NF-κB activation.
- Its in vivo function, particularly in liver injury, remains largely unknown.
Purpose of the Study:
- To investigate the in vivo role of Carma3 in liver injury.
- To determine the specific cell types and mechanisms involved in Carma3-mediated liver protection.
Main Methods:
- Established a concanavalin A (Con A)-induced autoimmune hepatitis model in Carma3 knockout (Carma3-/-) mice.
- Analyzed liver injury, liver sinusoidal endothelial cell (LSEC) damage, coagulation, and mitochondrial function in vitro and in vivo.
Main Results:
- Carma3-/- mice exhibited exacerbated liver injury and coagulation following Con A treatment.
- Carma3 expression was significantly higher in LSECs than hepatocytes.
- Carma3 deficiency led to increased LSEC damage, mitochondrial dysfunction, and cell death upon Con A exposure.
Conclusions:
- Carma3 plays a critical, previously unrecognized role in maintaining LSEC integrity and preventing liver injury.
- Targeting Carma3 may offer novel therapeutic strategies for toxic liver insults.
Related Concept Videos
01:24Liver Regeneration
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
01:30Liver Physiology
Metabolic Regulation:
The liver is the central organ involved in regulating blood composition. It stabilizes blood glucose levels, maintaining them within the range of 70–110 mg/dL. When these levels drop, the liver breaks down glycogen reserves and releases glucose into the bloodstream. It can...
01:21Hepatic Portal System
At its core, the hepatic portal vein is the result of a confluence of the superior and inferior mesenteric veins along with the splenic vein. Each of these veins has a unique role. The superior mesenteric vein is...