[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Tissue repair](https://durgical.com/en/general-pathology/#a-repair) › Fibrosis in organs: TGF-β and the myofibroblast

[General pathology](https://durgical.com/en/general-pathology/) · [Tissue repair](https://durgical.com/en/general-pathology/#a-repair)

# Fibrosis in organs: TGF-β and the myofibroblast

- Mechanism

When injury keeps coming back, organs fill with scar: TGF-β turns support cells into myofibroblasts that lay down collagen and stiffen the organ.

Updated 2026-11-01

## Key points

- TGF-β is the main fibrogenic cytokine; the myofibroblast makes the collagen.
- Liver: hepatic stellate (Ito) cells, which normally store vitamin A.
- Imbalance: more collagen synthesis and less breakdown by metalloproteinases (TIMPs rise).
- Fibrosis destroys architecture: cirrhosis, pulmonary fibrosis, chronic kidney disease, chronic pancreatitis.
- Early fibrosis can partly regress if the injury stops.

## What it is

Fibrosis is the excessive deposition of collagen and other matrix in an organ during chronic injury and inflammation. It uses the same machinery as wound scarring, but persistently and throughout the parenchyma, so it distorts the architecture and causes organ failure: cirrhosis, pulmonary fibrosis, chronic kidney disease, chronic pancreatitis. TGF-β is the main driver and the myofibroblast is the cell that makes the scar; stopping the injury can partly reverse early fibrosis.

## Key facts

- Hepatic stellate cells sit in the space of Disse and store vitamin A; when activated they lose it and become collagen-producing myofibroblasts.
- Fibrosis partly regresses when the cause stops early (for example after hepatitis C is cured), but advanced, heavily cross-linked scar changes little.
- In schistosomiasis, granulomas around eggs in portal vein branches cause periportal (pipe-stem) fibrosis and portal hypertension.

## Step by step

- Repeated injury (toxins, viruses, autoimmunity, ischaemia, obstruction) kills parenchymal cells and keeps inflammation going.
- Alternatively activated macrophages, lymphocytes, platelets and injured epithelium release TGF-β, PDGF and IL-13.
- TGF-β, freed from its latent form bound to the matrix, signals through SMAD proteins in resident cells.
- Fibroblasts, pericytes and, in the liver, hepatic stellate cells become myofibroblasts (alpha-smooth muscle actin).
- Myofibroblasts proliferate, contract and secrete type I and III collagen and fibronectin.
- TIMPs rise and metalloproteinase activity falls, so collagen accumulates faster than it is removed.
- Scar distorts the architecture, blocks blood flow and replaces working cells: the organ fails.

## Fibrosis by organ

| Organ | Common causes | Effector cell and result |
| --- | --- | --- |
| [Liver (cirrhosis)](https://durgical.com/en/conditions/cirrhosis/) | Hepatitis B and C, alcohol, metabolic fatty liver disease, autoimmune and biliary disease | Hepatic stellate (Ito) cells; nodules, portal hypertension, liver failure |
| [Lung (interstitial fibrosis)](https://durgical.com/en/conditions/interstitial-lung-disease/) | Idiopathic pulmonary fibrosis, pneumoconioses, systemic sclerosis, drugs, radiation | Fibroblasts; restrictive disease, honeycomb lung |
| [Kidney](https://durgical.com/en/conditions/chronic-kidney-disease/) | Diabetes, hypertension, glomerulonephritis, obstruction | Pericytes and fibroblasts; chronic kidney disease |
| [Pancreas](https://durgical.com/en/conditions/chronic-pancreatitis/) | Alcohol, smoking, duct obstruction, genetic causes | Pancreatic stellate cells; exocrine and endocrine insufficiency |
| Heart | Myocardial infarction, chronic Chagas disease, hypertension | Cardiac fibroblasts; stiff heart, arrhythmias, heart failure |
| [Skin and internal organs (systemic sclerosis)](https://durgical.com/en/conditions/systemic-sclerosis/) | Autoimmune vascular injury and fibroblast activation | Thick skin, lung and gut fibrosis |

## Clinical notes

- Antifibrotic drugs (pirfenidone, nintedanib) slow the loss of lung function in idiopathic pulmonary fibrosis.
- Elastography and blood-test scores estimate liver fibrosis without a biopsy.
- In Latin America, chronic Chagas disease causes myocardial fibrosis that leads to cardiomyopathy and conduction block.

## Memory aid

TGF-β is the foreman, the myofibroblast is the bricklayer, and the TIMPs hide the demolition tools.

## Test yourself

Think of the answer, then tap the question to see it.

## Which cell produces the fibrosis of the cirrhotic liver?

The hepatic stellate (Ito) cell, which, once activated, becomes a collagen-secreting myofibroblast.

## Which cytokine is the main driver of fibrosis?

TGF-β, which activates fibroblasts, stimulates collagen synthesis and inhibits matrix breakdown.

## Why does fibrosis cause organ failure?

Collagen replaces working cells and distorts architecture and blood flow, for example portal hypertension in cirrhosis or stiff lungs in pulmonary fibrosis.

[Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/fibrosis-in-organs-tgf-and-the-myofibroblast/)

## Related

- [Chronic inflammation: causes, cells and features](https://durgical.com/en/general-pathology/chronic-inflammation-causes-cells-and-features/)
- [Granulation tissue and scar formation](https://durgical.com/en/general-pathology/granulation-tissue-and-scar-formation/)
- [Liver regeneration](https://durgical.com/en/general-pathology/liver-regeneration/)
- [Tissue repair: regeneration or scar; labile, stable and permanent cells](https://durgical.com/en/general-pathology/tissue-repair-regeneration-or-scar-labile-stable-and-permanent-cells/)
- [Abnormal repair: chronic wounds, hypertrophic scar, keloid, contracture](https://durgical.com/en/general-pathology/abnormal-repair-chronic-wounds-hypertrophic-scar-keloid-contracture/)
- [Ionizing radiation injury](https://durgical.com/en/general-pathology/ionizing-radiation-injury/)

## Related conditions

- [Cirrhosis](https://durgical.com/en/conditions/cirrhosis/)
- [Interstitial lung disease](https://durgical.com/en/conditions/interstitial-lung-disease/)
- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)
- [Chronic pancreatitis](https://durgical.com/en/conditions/chronic-pancreatitis/)
- [Systemic sclerosis (scleroderma, including CREST)](https://durgical.com/en/conditions/systemic-sclerosis/)
- [Constrictive pericarditis](https://durgical.com/en/conditions/constrictive-pericarditis/)
- [Chagas cardiomyopathy](https://durgical.com/en/conditions/chagas-cardiomyopathy/)
- [Pneumoconioses (silicosis, asbestosis, coal workers' pneumoconiosis)](https://durgical.com/en/conditions/pneumoconioses/)
- [Myocardial Infarction (Heart Attack)](https://durgical.com/en/conditions/myocardial-infarction/)
- [Alcoholic liver disease (biochemistry)](https://durgical.com/en/conditions/alcoholic-liver-disease/)
- [Metabolic dysfunction-associated steatotic liver disease (MASLD/NAFLD)](https://durgical.com/en/conditions/metabolic-dysfunction-associated-steatotic-liver-disease/)
- [Schistosomiasis](https://durgical.com/en/conditions/schistosomiasis/)

## Elsewhere in DurgiPedia

- [Collagen](https://durgical.com/en/biochemistry/enzymes/collagen/)
- [Collagen synthesis](https://durgical.com/en/biochemistry/topics/collagen-synthesis/)
- [Extracellular matrix: collagen types, elastin, ground substance](https://durgical.com/en/histology/extracellular-matrix-collagen-types-elastin-ground-substance/)
- [IL-10 and TGF-β (the brakes)](https://durgical.com/en/immunology/il-10-and-tgf/)
- [IL-4, IL-5 and IL-13 (the Th2 cytokines)](https://durgical.com/en/immunology/il-4-il-5-and-il-13/)
- [Liver: lobule, acinus, hepatocytes, sinusoids, Kupffer cells](https://durgical.com/en/histology/liver-lobule-acinus-hepatocytes-sinusoids-kupffer-cells/)

## Microorganisms

- [Schistosoma mansoni / S. haematobium / S. japonicum](https://durgical.com/en/microbiology/schistosoma-mansoni-s-haematobium-s-japonicum/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Cirrhosis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000255.htm) (MedlinePlus, US National Library of Medicine, 2026); [Pulmonary Fibrosis | Idiopathic Pulmonary Fibrosis | IPF | MedlinePlus](https://medlineplus.gov/pulmonaryfibrosis.html) (MedlinePlus, US National Library of Medicine, 2026); [Hepatic Cirrhosis](https://www.ncbi.nlm.nih.gov/books/NBK482419/) (StatPearls (NCBI Bookshelf), 2024); [Chronic Pancreatitis](https://www.ncbi.nlm.nih.gov/books/NBK482325/) (StatPearls (NCBI Bookshelf), 2024).

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/general-pathology/fibrosis-in-organs-tgf-and-the-myofibroblast/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/fibrosis-in-organs-tgf-and-the-myofibroblast/