Related Experiment Video

Updated: Aug 5, 2026

Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
07:46

Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation

Published on: April 3, 2017

Macrophage FOLR2 drives liver fibrosis via intercellular engagement of TGFβRII

Man-Man Yuan1, Bing-Feng Zheng1, Jing-Lin Wang2

  • 1State Key Laboratory of Pharmaceutical Biotechnology, Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, School of Life Sciences, Nanjing University, Nanjing, 210093, China.

Acta Pharmacologica Sinica
|July 30, 2026
PubMed

Insights

Targeting folate receptor beta (Folr2) on macrophages disrupts communication with hepatic stellate cells (HSCs), reducing liver fibrosis. Fraxinellone, a natural compound, blocks this interaction, offering a potential therapy.

Area of Science:

  • Cell Biology
  • Immunology
  • Hepatology

Background:

  • Liver fibrosis involves hepatic stellate cells (HSCs) and macrophages.
  • Direct communication between these cells during fibrosis is not fully understood.

Purpose of the Study:

  • To investigate the role of folate receptor beta (Folr2) in macrophage-HSC crosstalk during liver fibrosis.
  • To identify therapeutic targets for liver fibrosis.

Main Methods:

  • Genetic deletion of Folr2 in mice.
  • Immunohistochemistry on human and murine fibrotic liver samples.
  • Co-culture assays to assess HSC activation.
  • Molecular analysis of TGF-β signaling.
  • Treatment with the natural compound fraxinellone.

Main Results:

  • Genetic deletion of Folr2 attenuated experimental liver fibrosis.
  • FOLR2-expressing macrophages were found near activated HSCs in fibrotic livers.
  • FOLR2 on reparative macrophages promoted HSC activation via contact-dependent mechanisms.
  • FOLR2 binds to TGFβRII on HSCs, sustaining TGF-β1 signaling.
  • Fraxinellone disrupted the FOLR2-TGFβRII interaction, reducing HSC activation and fibrosis.

Conclusions:

  • The FOLR2-TGFβRII interaction is crucial for macrophage-HSC crosstalk in liver fibrosis.
  • Targeting this interaction, for example with fraxinellone, is a potential therapeutic strategy for liver fibrosis.
Keywords:
FOLR2TGFβRIIintercellular interactionliver fibrosisreparative macrophage

More Related Videos

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool10:15

Rapid Depletion of Renal Macrophages Using Human CD59/Intermedilysin Cell Ablation Tool

Published on: May 9, 2025

Related Concept Videos

Cirrhosis II: Pathophysiology01:24

Cirrhosis II: Pathophysiology

Cirrhosis is a progressive chronic liver injury caused by prolonged inflammation, excessive fibrotic remodeling, and impaired regeneration. Over time, repeated hepatic insults disrupt the liver’s architecture and function, leading to reduced blood flow, impaired bile drainage, and diminished metabolic capacity.Pathophysiology of cirrhosisCirrhosis arises from three main responses to chronic liver damage: inflammation, immune activation, and hepatocyte death. These processes lead to structural...
Chronic Inflammation: Introduction01:12

Chronic Inflammation: Introduction

Chronic inflammation is a prolonged, dysregulated immune response that persists for weeks to years when the inciting stimulus is difficult to eradicate or when self‑antigens drive ongoing reactivity. Morphologically, it is defined by mononuclear cell infiltration, progressive tissue destruction, and concurrent attempts at healing via angiogenesis and fibrosis. Compared with acute inflammation, edema is less prominent while cellular infiltration predominates; triggers include persistent...
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 large...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

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 are of three kinds RI, RII, and RIII. The RI...
Cirrhosis I: Introduction01:23

Cirrhosis I: Introduction

Cirrhosis is a chronic, irreversible liver disease characterized by the widespread replacement of healthy liver tissue with fibrotic scar tissue and the formation of regenerative nodules.Etiology of cirrhosisCirrhosis results from sustained liver injury that triggers progressive fibrosis and structural remodeling. The underlying causes are diverse, encompassing common and less frequent clinical conditions. Regardless of the origin, all causes lead to chronic inflammation, hepatocyte loss, and...
Inflammation01:38

Inflammation

Overview