RUNX1 promotes liver fibrosis progression through regulating TGF-β signalling
Zhaoyang Guo1,2, Xinxin Liu3, Shulei Zhao4
1Department of Infectious Diseases, Shandong Provincial Hospital, Shandong University, Jinan, China.
International Journal of Experimental Pathology
|April 18, 2023
Summary
RUNX1 is upregulated in liver fibrosis and worsens the condition by activating TGF-β/Smads signaling. This suggests RUNX1 as a potential therapeutic target for treating liver fibrosis.
Area of Science:
- Hepatology
- Molecular Biology
- Cell Biology
Background:
- Liver fibrosis results from chronic liver injury, with unclear pathogenesis and limited treatment options.
- Identifying novel therapeutic targets is crucial for managing liver fibrosis.
Purpose of the Study:
- To investigate the role of RUNX1 in liver fibrosis.
- To explore RUNX1 as a potential therapeutic target for liver fibrosis.
Main Methods:
- Carbon tetrachloride (CCl4)-induced liver fibrosis mouse model.
- Primary hepatic stellate cell isolation and immunofluorescence staining.
- Dual-luciferase reporter assay and Western blotting for signal pathway analysis.
Main Results:
- RUNX1 expression was significantly upregulated in cirrhotic liver tissues.
- Overexpression of RUNX1 exacerbated liver fibrosis and increased α-SMA expression.
- RUNX1 activation of TGF-β/Smads signaling was confirmed via dual-luciferase reporter assay.
Conclusions:
- RUNX1 acts as a novel regulator of hepatic fibrosis by activating TGF-β/Smads signaling.
- RUNX1 represents a promising therapeutic target for liver fibrosis treatment.
- This study offers new insights into the etiology of liver fibrosis.
More Related Videos
10:21Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
7.2K
10:42Development of an Ethanol-induced Fibrotic Liver Model in Zebrafish to Study Progenitor Cell-mediated Hepatocyte Regeneration
Published on: May 13, 2016
9.2K
Related Concept Videos
01:16TGF - β Signaling Pathway
7.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.5K
01:22PI3K/mTOR/AKT Signaling Pathway
3.8K
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...
3.8K
01:24Regulation of Angiogenesis and Blood Supply
2.6K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K
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
02:54Canonical Wnt Signaling Pathway
8.8K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.8K
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