Resolution of organ fibrosis

Abstract

Fibrosis is the excessive accumulation of extracellular matrix that often occurs as a wound healing response to repeated or chronic tissue injury, and may lead to the disruption of organ architecture and loss of function. Although fibrosis was previously thought to be irreversible, recent evidence indicates that certain circumstances permit the resolution of fibrosis when the underlying causes of injury are eradicated. The mechanism of fibrosis resolution encompasses degradation of the fibrotic extracellular matrix as well as elimination of fibrogenic myofibroblasts through their adaptation of various cell fates, including apoptosis, senescence, dedifferentiation, and reprogramming. In this Review, we discuss the present knowledge and gaps in our understanding of how matrix degradation is regulated and how myofibroblast cell fates can be manipulated, areas that may identify potential therapeutic approaches for fibrosis.

Towards better definition, quantification and treatment of fibrosis in heart failure. A scientific roadmap by the Committee of Translational Research of the Heart Failure Association (HFA) of the European Society of Cardiology

“…So, it seems that in certain forms and stages of heart failure the fibrotic response cannot be switched off, and that a certain degree of fibrogenesis remains persistent. This is different from physiological healing, where the termination of the reparative phase is identified by the disappearance of activated myofibroblasts from the tissue …”

“…This is different from physiological healing, where the termination of the reparative phase is identified by the disappearance of activated myofibroblasts from the tissue. 32,33 It is currently unknown how to differentiate the endogenous, necessary and beneficial fibrotic response or matrix turnover from the excessive, ongoing and harmful chronic fibrotic response that leads to matrix deposition and tissue stiffening. 34 We postulate that these triggers that cause this chronic fibrotic response are multifold, including sustained fibroblast proliferation via feedback loops, cardiomyocyte-mediated fibroblast activation, inhibition of myofibroblast apoptosis, and the presence of sustained low-grade systemic and local inflammation.…”

A Deactivation Factor of Fibrogenic Hepatic Stellate Cells Induces Regression of Liver Fibrosis in Mice

“…Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis, which is caused by chronic infection with hepatitis viruses B and C, excessive alcohol intake, and nonalcoholic steatohepatitis. (1,2) HSCs are activated by inflammatory stimuli, such as transforming growth factor-β (TGF-β), platelet-derived growth factor, and chemokines, and are converted into α-smooth muscle actin (αSMA)-expressing myofibroblast-like cells. (3,4) Liver fibrosis was originally considered to be a progressive and irreversible condition.…”

“…It eventually leads to liver cirrhosis, which causes hepatic functional failure and portal hypertension and provides a pathological background for the development of hepatocellular carcinoma. Hepatic stellate cells (HSCs) play a central role in the development of liver fibrosis, which is caused by chronic infection with hepatitis viruses B and C, excessive alcohol intake, and nonalcoholic steatohepatitis . HSCs are activated by inflammatory stimuli, such as transforming growth factor‐β (TGF‐β), platelet‐derived growth factor, and chemokines, and are converted into α‐smooth muscle actin (αSMA)‐expressing myofibroblast‐like cells …”

Achilles tendinopathy – pathophysiology: state of the art

“…After a healing process is completed, the mechanical stress will be released on the myofibroblasts, which subsequently undergo programmed cell death (apoptosis). If this mechanism fails, the myofibroblasts will propagate a hyperproliferative process, resulting in fibrosis,83 which is observed as a prominent histological feature of tendinopathy (figure 3). …”