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Short description: Excess connective tissue in healing
Cardiac amyloidosis very high mag movat.jpg
Micrograph of a heart showing fibrosis (yellow – left of image) and amyloid deposition (brown – right of image). Movat's stain.
SpecialtyPathology, rheumatology
Risk factorsRepeated injuries, chronic inflammation.[1]

Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of permanent scar tissue.[1][2]

Repeated injuries, chronic inflammation and repair are susceptible to fibrosis where an accidental excessive accumulation of extracellular matrix components, such as the collagen is produced by fibroblasts, leading to the formation of a permanent fibrotic scar.[1]

In response to injury, this is called scarring, and if fibrosis arises from a single cell line, this is called a fibroma. Physiologically, fibrosis acts to deposit connective tissue, which can interfere with or totally inhibit the normal architecture and function of the underlying organ or tissue. Fibrosis can be used to describe the pathological state of excess deposition of fibrous tissue, as well as the process of connective tissue deposition in healing.[3] Defined by the pathological accumulation of extracellular matrix (ECM) proteins, fibrosis results in scarring and thickening of the affected tissueit is in essence an exaggerated wound healing response which interferes with normal organ function.[4]


Fibrosis is similar to the process of scarring, in that both involve stimulated fibroblasts laying down connective tissue, including collagen and glycosaminoglycans. The process is initiated when immune cells such as macrophages release soluble factors that stimulate fibroblasts. The most well characterized pro-fibrotic mediator is TGF beta, which is released by macrophages as well as any damaged tissue between surfaces called interstitium. Other soluble mediators of fibrosis include CTGF, platelet-derived growth factor (PDGF), and interleukin 10 (IL-10). These initiate signal transduction pathways such as the AKT/mTOR[5] and SMAD[6] pathways that ultimately lead to the proliferation and activation of fibroblasts, which deposit extracellular matrix into the surrounding connective tissue. This process of tissue repair is a complex one, with tight regulation of extracellular matrix (ECM) synthesis and degradation ensuring maintenance of normal tissue architecture. However, the entire process, although necessary, can lead to a progressive irreversible fibrotic response if tissue injury is severe or repetitive, or if the wound healing response itself becomes deregulated.[4][7]

Anatomical location

Fibrosis can occur in many tissues within the body, typically as a result of inflammation or damage, and examples include:

Micrograph showing cirrhosis of the liver. The tissue in this example is stained with a trichrome stain, in which fibrosis is colored blue. The red areas are the nodular liver tissue



  • Bridging fibrosis An advanced stage of liver fibrosis seen in the progressive form of chronic liver diseases. The term “bridging” means ‘the formation of “bridge” (by the band of mature & thick fibrous tissue) obliterating portal area to central vein’, leads to the formation of pseudolobules. Long-term exposure to hepatotoxin (e.g. thioacetamide, carbon tetrachloride, diethylnitrosamine) results in the bridging fibrosis in experimental animal models.[8]
  • Senescence of hepatic stellate cells could prevent progression of liver fibrosis, although this has not been implemented as a therapy, and would carry the risk of hepatic dysfunction.[9]
Bridging fibrosis in a Wistar rat following a six-week course of thioacetamide. Sirius Red stain



  • Glial scar


Myocardial fibrosis has mainly two forms:

  • Interstitial fibrosis, which has been described in congestive heart failure, hypertension, and normal aging.[11]
  • Replacement fibrosis, which indicates an older myocardial infarction.[11]



  1. 1.0 1.1 1.2 Wynn, Thomas A. (2004). "Fibrotic disease and the TH1/TH2 paradigm". Nature Reviews. Immunology (Springer Science and Business Media LLC) 4 (8): 583–594. doi:10.1038/nri1412. ISSN 1474-1733. PMID 15286725. 
  2. Birbrair, Alexander; Zhang, Tan; Files, Daniel C.; Mannava, Sandeep; Smith, Thomas; Wang, Zhong-Min; Messi, Maria L.; Mintz, Akiva et al. (2014-11-06). "Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner" (in en). Stem Cell Research & Therapy 5 (6): 122. doi:10.1186/scrt512. ISSN 1757-6512. PMID 25376879. 
  3. Glossary of dermatopathological terms. DermNet NZ
  4. 4.0 4.1 "Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis". Fibrogenesis & Tissue Repair 8: 18. 2015. doi:10.1186/s13069-015-0035-8. PMID 26435749. 
  5. "Dual mTOR Inhibition Is Required to Prevent TGF-β-Mediated Fibrosis: Implications for Scleroderma.". J Invest Dermatol 135 (11): 2873–6. 2015. doi:10.1038/jid.2015.252. PMID 26134944. 
  6. "TGF-beta signaling and the fibrotic response". FASEB Journal 18 (7): 816–827. 2004. doi:10.1096/fj.03-1273rev. PMID 15117886. 
  7. Meyer, Keith C. (May 2017). "Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis". Expert Review of Respiratory Medicine 11 (5): 343–359. doi:10.1080/17476348.2017.1312346. ISSN 1747-6356. PMID 28345383. 
  8. dwivedi, durgesh Kumar; Jena, Gopa Bandhu (Nov 2018). "Glibenclamide protects against thioacetamide-induced hepatic damage in Wistar rat: investigation on NLRP3, MMP-2, and stellate cell activation". Naunyn-Schmiedeberg's Archives of Pharmacology 391 (11): 1257–1274. doi:10.1007/s00210-018-1540-2. PMID 30066023. 
  9. "Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives". Mechanisms of Ageing and Development 199: 111572. 2021. doi:10.1016/j.mad.2021.111572. PMID 34536446. 
  10. "Cellular senescence in the aging and diseased kidney". Journal of Cell Communication and Signaling 12 (1): 69–82. 2018. doi:10.1007/s12079-017-0434-2. PMID 29260442. 
  11. 11.0 11.1 Chute, Michael; Aujla, Preetinder; Jana, Sayantan; Kassiri, Zamaneh (2019). "The Non-Fibrillar Side of Fibrosis: Contribution of the Basement Membrane, Proteoglycans, and Glycoproteins to Myocardial Fibrosis". Journal of Cardiovascular Development and Disease 6 (4): 35. doi:10.3390/jcdd6040035. ISSN 2308-3425. PMID 31547598. 
  12. "Cellular and molecular mechanisms in kidney fibrosis". J Clin Invest 124 (6): 2299–306. June 2014. doi:10.1172/JCI72267. PMID 24892703. 

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