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Wikipedia

Fibrosis

July 30, 2023

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]

Fibrosis
Micrograph of a heart showing fibrosis (yellow – left of image) and amyloid deposition (brown – right of image). Movat's stain.
SpecialtyPathology, rheumatology
ComplicationsCirrhosis
Risk factorsRepeated injuries, chronic inflammation.[1]

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 tissue — it is in essence an exaggerated wound healing response which interferes with normal organ function.[4]

Physiology

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

Lungs

Liver

  • 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

Kidney

Brain

Heart

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]
  •  

    Healthy myocardium versus interstitial fibrosis in dilated cardiomyopathy. Alcian blue stain.

  •  

    Replacement fibrosis in myocardial infarction, being boundless and dense.

Other

References

  1. ^ a b c Wynn TA (August 2004). "Fibrotic disease and the T(H)1/T(H)2 paradigm". Nature Reviews. Immunology. Springer Science and Business Media LLC. 4 (8): 583–594. doi:10.1038/nri1412. PMC 2702150. PMID 15286725.
  2. ^ Birbrair A, Zhang T, Files DC, Mannava S, Smith T, Wang ZM, et al. (November 2014). "Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner". Stem Cell Research & Therapy. 5 (6): 122. doi:10.1186/scrt512. PMC 4445991. PMID 25376879.
  3. ^ "Glossary of dermatopathological terms". DermNet NZ.
  4. ^ a b Neary R, Watson CJ, Baugh JA (2015). "Epigenetics and the overhealing wound: the role of DNA methylation in fibrosis". Fibrogenesis & Tissue Repair. 8: 18. doi:10.1186/s13069-015-0035-8. PMC 4591063. PMID 26435749.
  5. ^ Mitra A, Luna JI, Marusina AI, Merleev A, Kundu-Raychaudhuri S, Fiorentino D, et al. (November 2015). "Dual mTOR Inhibition Is Required to Prevent TGF-β-Mediated Fibrosis: Implications for Scleroderma". The Journal of Investigative Dermatology. 135 (11): 2873–2876. doi:10.1038/jid.2015.252. PMC 4640976. PMID 26134944.
  6. ^ Leask A, Abraham DJ (May 2004). "TGF-beta signaling and the fibrotic response". FASEB Journal. 18 (7): 816–827. CiteSeerX 10.1.1.314.4027. doi:10.1096/fj.03-1273rev. PMID 15117886. S2CID 2027993.
  7. ^ Meyer KC (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. PMID 28345383. S2CID 42073964.
  8. ^ Dwivedi DK, Jena GB (November 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. S2CID 51890984.
  9. ^ Zhang M, Serna-Salas S, Damba T, Borghesan M, Demaria M, Moshage H (October 2021). "Hepatic stellate cell senescence in liver fibrosis: Characteristics, mechanisms and perspectives". Mechanisms of Ageing and Development. 199: 111572. doi:10.1016/j.mad.2021.111572. PMID 34536446. S2CID 237524296.
  10. ^ Valentijn FA, Falke LL, Nguyen TQ, Goldschmeding R (March 2018). "Cellular senescence in the aging and diseased kidney". Journal of Cell Communication and Signaling. 12 (1): 69–82. doi:10.1007/s12079-017-0434-2. PMC 5842195. PMID 29260442.
  11. ^ a b Chute M, Aujla P, Jana S, Kassiri Z (September 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. PMC 6956278. PMID 31547598.
  12. ^ Duffield JS (June 2014). "Cellular and molecular mechanisms in kidney fibrosis". The Journal of Clinical Investigation. 124 (6): 2299–2306. doi:10.1172/JCI72267. PMC 4038570. PMID 24892703.
  13. ^ Nelson FR, Blauvelt CT (January 2015). "Chapter 2 - Musculoskeletal Diseases and Related Terms". A Manual of Orthopaedic Terminology (Eighth ed.). Philadelphia: W.B. Saunders. pp. 43–104. doi:10.1016/B978-0-323-22158-0.00002-0. ISBN 978-0-323-22158-0.

External links

  •   Media related to Fibrosis at Wikimedia Commons

July 30, 2023
fibrosis, also, known, fibrotic, scarring, pathological, wound, healing, which, connective, tissue, replaces, normal, parenchymal, tissue, extent, that, goes, unchecked, leading, considerable, tissue, remodelling, formation, permanent, scar, tissue, micrograph. 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 FibrosisMicrograph of a heart showing fibrosis yellow left of image and amyloid deposition brown right of image Movat s stain SpecialtyPathology rheumatologyComplicationsCirrhosisRisk factorsRepeated injuries chronic inflammation 1 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 tissue it is in essence an exaggerated wound healing response which interferes with normal organ function 4 Contents 1 Physiology 2 Anatomical location 2 1 Lungs 2 2 Liver 2 3 Kidney 2 4 Brain 2 5 Heart 2 6 Other 3 References 4 External linksPhysiology EditFibrosis 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 EditFibrosis 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 tissueLungs Edit Fibrothorax Pulmonary fibrosis Cystic fibrosis Idiopathic pulmonary fibrosis idiopathic meaning the cause is unknown Radiation induced lung injury following treatment for cancer Liver Edit 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 amp 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 stainCirrhosisKidney Edit CYR61 induction of cellular senescence in the kidney is a potential therapy to limit fibrosis 10 Brain Edit Glial scarHeart Edit 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 Healthy myocardium versus interstitial fibrosis in dilated cardiomyopathy Alcian blue stain Replacement fibrosis in myocardial infarction being boundless and dense Other Edit Arterial stiffness Arthrofibrosis knee shoulder other joints Chronic kidney disease 12 Crohn s disease intestine Dupuytren s contracture hands fingers Keloid skin Lipedema fat cells typically in lower limbs Mediastinal fibrosis soft tissue of the mediastinum Myelofibrosis bone marrow Myofibrosis skeletal muscle 13 Peyronie s disease penis Nephrogenic systemic fibrosis skin Progressive massive fibrosis lungs a complication of coal workers pneumoconiosis Retroperitoneal fibrosis soft tissue of the retroperitoneum Scleroderma systemic sclerosis skin lungs Some forms of adhesive capsulitis shoulder References Edit a b c Wynn TA August 2004 Fibrotic disease and the T H 1 T H 2 paradigm Nature Reviews Immunology Springer Science and Business Media LLC 4 8 583 594 doi 10 1038 nri1412 PMC 2702150 PMID 15286725 Birbrair A Zhang T Files DC Mannava S Smith T Wang ZM et al November 2014 Type 1 pericytes accumulate after tissue injury and produce collagen in an organ dependent manner Stem Cell Research amp Therapy 5 6 122 doi 10 1186 scrt512 PMC 4445991 PMID 25376879 Glossary of dermatopathological terms DermNet NZ a b Neary R Watson CJ Baugh JA 2015 Epigenetics and the overhealing wound the role of DNA methylation in fibrosis Fibrogenesis amp Tissue Repair 8 18 doi 10 1186 s13069 015 0035 8 PMC 4591063 PMID 26435749 Mitra A Luna JI Marusina AI Merleev A Kundu Raychaudhuri S Fiorentino D et al November 2015 Dual mTOR Inhibition Is Required to Prevent TGF b Mediated Fibrosis Implications for Scleroderma The Journal of Investigative Dermatology 135 11 2873 2876 doi 10 1038 jid 2015 252 PMC 4640976 PMID 26134944 Leask A Abraham DJ May 2004 TGF beta signaling and the fibrotic response FASEB Journal 18 7 816 827 CiteSeerX 10 1 1 314 4027 doi 10 1096 fj 03 1273rev PMID 15117886 S2CID 2027993 Meyer KC 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 PMID 28345383 S2CID 42073964 Dwivedi DK Jena GB November 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 S2CID 51890984 Zhang M Serna Salas S Damba T Borghesan M Demaria M Moshage H October 2021 Hepatic stellate cell senescence in liver fibrosis Characteristics mechanisms and perspectives Mechanisms of Ageing and Development 199 111572 doi 10 1016 j mad 2021 111572 PMID 34536446 S2CID 237524296 Valentijn FA Falke LL Nguyen TQ Goldschmeding R March 2018 Cellular senescence in the aging and diseased kidney Journal of Cell Communication and Signaling 12 1 69 82 doi 10 1007 s12079 017 0434 2 PMC 5842195 PMID 29260442 a b Chute M Aujla P Jana S Kassiri Z September 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 PMC 6956278 PMID 31547598 Duffield JS June 2014 Cellular and molecular mechanisms in kidney fibrosis The Journal of Clinical Investigation 124 6 2299 2306 doi 10 1172 JCI72267 PMC 4038570 PMID 24892703 Nelson FR Blauvelt CT January 2015 Chapter 2 Musculoskeletal Diseases and Related Terms A Manual of Orthopaedic Terminology Eighth ed Philadelphia W B Saunders pp 43 104 doi 10 1016 B978 0 323 22158 0 00002 0 ISBN 978 0 323 22158 0 External links Edit Media related to Fibrosis at Wikimedia Commons Retrieved from https en wikipedia org w index php title Fibrosis amp oldid 1155222609, wikipedia, wiki, book, books, library,

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