Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Oct 15;10(10):2759.
doi: 10.3390/cells10102759.

Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression

Alessandra Caligiuri  1 , Alessandra Gentilini  1 , Mirella Pastore  1 , Stefano Gitto  1 , Fabio Marra  1
Affiliations
Review

Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression

Alessandra Caligiuri et al. Cells. .

Abstract

Chronic liver injury of different etiologies may result in hepatic fibrosis, a scar formation process consisting in altered deposition of extracellular matrix. Progression of fibrosis can lead to impaired liver architecture and function, resulting in cirrhosis and organ failure. Although fibrosis was previous thought to be an irreversible process, recent evidence convincingly demonstrated resolution of fibrosis in different organs when the cause of injury is removed. In the liver, due to its high regenerative ability, the extent of fibrosis regression and reversion to normal architecture is higher than in other tissues, even in advanced disease. The mechanisms of liver fibrosis resolution can be recapitulated in the following main points: removal of injurious factors causing chronic hepatic damage, elimination, or inactivation of myofibroblasts (through various cell fates, including apoptosis, senescence, and reprogramming), inactivation of inflammatory response and induction of anti-inflammatory/restorative pathways, and degradation of extracellular matrix. In this review, we will discuss the major cellular and molecular mechanisms underlying the regression of fibrosis/cirrhosis and the potential therapeutic approaches aimed at reversing the fibrogenic process.

Keywords: ECM degradation; HSCs; fibrosis regression; liver fibrosis; myofibroblasts; therapies.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the mechanisms underlying liver fibrosis regression. Four main mechanisms underlying the regression process of liver fibrosis are indicated. Hepatic stellate cells (HSCs); TNF receptor 1 (TNFR1); insulin-like growth factor I (IGF-I); transcription factor 21 (Tcf21); natural killer cells (NK); activated HSCs (aHSCs); inactivated HSCs (iHSCs); extracellular matrix (ECM); NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3); matrix metalloproteases (MMPs); Kupffer cells (KCs); vascular endothelial growth factor (VEGF); tissue inhibitors of MMPs (TIMPs).
See this image and copyright information in PMC

References

    1. Pinzani M., Rombouts K., Colagrande S. Fibrosis in chronic liver diseases: Diagnosis and management. J. Hepatol. 2005;42((Suppl. 1)):S22–S36. doi: 10.1016/j.jhep.2004.12.008. - DOI - PubMed
    1. Khurana A., Sayed N., Allawadhi P., Weiskirchen R. It’s all about the spaces between cells: Role of extracellular matrix in liver fibrosis. Ann. Transl. Med. 2021;9:728. doi: 10.21037/atm-20-2948. - DOI - PMC - PubMed
    1. Zoubek M.E., Trautwein C., Strnad P. Reversal of liver fibrosis: From fiction to reality. Best Pract. Res. Clin. Gastroenterol. 2017;31:129–141. doi: 10.1016/j.bpg.2017.04.005. - DOI - PubMed
    1. Tacke F., Trautwein C. Mechanisms of liver fibrosis resolution. J. Hepatol. 2015;63:1038–1039. doi: 10.1016/j.jhep.2015.03.039. - DOI - PubMed
    1. Weiskirchen R., Weiskirchen S., Tacke F. Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications. Mol. Asp. Med. 2019;65:2–15. doi: 10.1016/j.mam.2018.06.003. - DOI - PubMed

Publication types