Related Experiment Video

Updated: Sep 19, 2025

Cell Type-specific Gene Expression Profiling in the Mouse Liver
10:06

Cell Type-specific Gene Expression Profiling in the Mouse Liver

Published on: September 17, 2019

7.8K

MFAP4 Deficiency Attenuates Liver Fibrosis by Regulating Hepatic Stellate Cell Fate Through Inhibition of the

Linxiang Liu1, Bimin Li1, Yue Zhang1

  • 1Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.

Cellular and Molecular Gastroenterology and Hepatology
|May 31, 2025
PubMed
Abstract

Insights

Microfibrillar-associated protein 4 (MFAP4) drives liver fibrosis by activating hepatic stellate cells (HSCs) through integrin αvβ3. Targeting MFAP4 shows promise in mitigating liver fibrosis by altering HSC fate.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Hepatology

Background:

  • Liver fibrosis results from chronic liver injury and involves hepatic stellate cell (HSC) activation.
  • Microfibrillar-associated protein 4 (MFAP4) is upregulated in liver fibrosis, but its precise role is unknown.

Purpose of the Study:

  • To elucidate the mechanistic role of MFAP4 in liver fibrosis.
  • To investigate MFAP4's impact on HSC activation, apoptosis, and fibrosis progression.

Main Methods:

  • Induction of liver fibrosis in wild-type and Mfpa4 knockout mice (CCl4, TAA models).
  • Activation of LX-2 cells with TGF-β1.
  • Utilized bioinformatics, scRNA-seq, histopathology, immunofluorescence, flow cytometry, Transwell cocultures, Western blot, and qPCR.

Main Results:

  • MFAP4 is expressed in HSCs and drives fibrosis primarily through HSCs.
  • MFAP4 inhibition reduces HSC activation, proliferation, and migration; overexpression has opposite effects.
  • MFAP4 binds integrin αvβ3 on HSCs, activating the FAK/PI3K/NFκB pathway, promoting HSC survival and fibrosis.
  • MFAP4 knockout alleviates liver fibrosis in mouse models.

Conclusions:

  • MFAP4 promotes HSC activation and apoptosis resistance via integrin αvβ3-dependent signaling.
  • Targeting MFAP4 offers a potential therapeutic strategy to mitigate liver fibrosis by modulating HSC behavior.
Keywords:
Cell FateHepatic Stellate CellIntegrinLiver FibrosisMFAP4

More Related Videos

Development of an Ethanol-induced Fibrotic Liver Model in Zebrafish to Study Progenitor Cell-mediated Hepatocyte Regeneration10:42

Development of an Ethanol-induced Fibrotic Liver Model in Zebrafish to Study Progenitor Cell-mediated Hepatocyte Regeneration

Published on: May 13, 2016

9.3K
Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration10:43

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration

Published on: May 19, 2016

6.8K

Related Concept Videos

Liver Regeneration01:24

Liver Regeneration

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...
3.4K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

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...
9.3K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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...
4.0K