Related Experiment Video
Updated: Jun 29, 2025
12:36
Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology
Published on: March 14, 2020
15.9K
Novel protein C6ORF120 promotes liver fibrosis by activating hepatic stellate cells through the PI3K/Akt/mTOR pathway
Xin Wang1, Hui Liu2, Yuqi Wang3
1Department of Center of Integrated Traditional Chinese and Western Medicine, Peking University Ditan Teaching Hospital, Beijing, China.
Journal of Gastroenterology and Hepatology
|March 25, 2024
Summary
C6ORF120 promotes liver fibrosis by activating hepatic stellate cells. This occurs through the PI3K/Akt/mTOR signaling pathway, as shown in knockout rats and cell models.
Area of Science:
- Hepatology
- Molecular Biology
- Cell Biology
Background:
- Hepatic fibrosis is a significant health concern.
- C6ORF120's role in liver fibrosis is not well understood.
Purpose of the Study:
- To investigate the role of C6ORF120 in carbon tetrachloride (CCL4)-induced hepatic fibrosis.
- To elucidate the underlying molecular mechanisms involving hepatic stellate cell activation.
Main Methods:
- Utilized C6orf120 knockout rats (C6orf120-/-) and LX-2 human hepatic stellate cells.
- Administered CCL4 to induce liver fibrosis in vivo.
- Stimulated LX-2 cells with recombinant C6ORF120 (rC6ORF120) in vitro.
- Employed Sirius Red, Masson staining, western blotting, PCR, immunohistochemistry, and immunofluorescence.
Main Results:
- C6orf120-/- rats exhibited reduced fibrosis and liver injury.
- RNA-seq analysis showed decreased extracellular matrix deposition and stellate cell activation in knockout rats.
- rC6ORF120 stimulated LX-2 cell activation, mirroring in vivo findings.
- Mechanistic studies identified elevated p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR levels.
- LY294002, a PI3K/Akt/mTOR inhibitor, reversed C6ORF120-induced LX-2 cell activation.
Conclusions:
- C6ORF120 activates hepatic stellate cells.
- C6ORF120 promotes hepatic fibrosis.
- The PI3K/Akt/mTOR signaling pathway mediates C6ORF120's pro-fibrotic effects.
Related Concept Videos
01:22PI3K/mTOR/AKT Signaling Pathway
3.5K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.5K
01:24Liver Regeneration
3.3K
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
3.3K
03:03mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
01:20The JAK-STAT Signaling Pathway
8.9K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.9K
01:58Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
01:24Chronic Pancreatitis I: Introduction
87
The pancreas, an elongated and flat gland situated behind the stomach, serves a vital function in digesting food and managing blood sugar levels.
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
87