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
. 2016 Mar;4(1):11-18.
doi: 10.1007/s40139-016-0099-1. Epub 2016 Feb 5.

Fibroblast-Extracellular Matrix Interactions in Tissue Fibrosis

Nikolaos G Frangogiannis  1
Affiliations

Fibroblast-Extracellular Matrix Interactions in Tissue Fibrosis

Nikolaos G Frangogiannis. Curr Pathobiol Rep. 2016 Mar.

Abstract

Activated myofibroblasts are key effector cells in tissue fibrosis. Emerging evidence suggests that myofibroblasts infiltrating fibrotic tissues originate predominantly from local mesenchyme-derived populations. Alterations in the extracellular matrix network play an important role in modulating fibroblast phenotype and function. In a pro-inflammatory environment, generation of matrix fragments may induce a matrix-degrading fibroblast phenotype. Deposition of ED-A fibronectin plays an important role in myofibroblast transdifferentiation. In fibrotic tissues, the matrix is enriched with matricellular macromolecules that regulate growth factor-mediated responses and modulate protease activation. This manuscript discusses emerging concepts on the role of the extracellular matrix in regulation of fibroblast behavior.

Keywords: Extracellular matrix; Fibroblast; Matricellular protein; Myofibroblast; Pericyte; Thrombospondin.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Nikolaos G Frangogiannis declares no conflict of interest.

Figures

Fig. 1
Fig. 1
Activated myofibroblasts are the main effector cells in tissue fibrosis. Left Immunofluorescent staining for α-smooth muscle actin identifies myofibroblasts in the infarcted heart. These cells are localized in the infarct border zone (arrows) and produce large amounts of extracellular matrix proteins. Right Myofibroblast conversion is mediated through activation of TGF-β signaling cascades and involves components of the extracellular matrix (ED-A fibronectin, hyaluronan, non-fibrillar collagens, etc.)
Fig. 2
Fig. 2
Alterations in the extracellular matrix network modulate fibroblast phenotype. a In a pro-inflammatory environment, collagen (Col), fibronectin (Fn), and low-molecular weight hyaluronan (LMWH) fragments stimulate a matrix-degrading fibroblast phenotype and may induce expression of pro-inflammatory mediators. b In fibrotic tissues, the extracellular matrix is enriched with matricellular proteins. These macromolecules do not play a structural role, but bind to growth factors and cell surface receptors and transduce signaling responses. For example, the prototypical matricellular protein thrombospondin (TSP)-1 is deposited into the matrix and modulates fibroblast function by facilitating the release of bioactive TGF-β (through a direct interaction with the latency-associated peptide/LAP), and by modulating growth factor (GF)- and integrin (ITG)-mediated responses. Some of the effects of TSP-1 may be mediated through activation of CD36 signaling
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214:199–210. - PMC - PubMed
    1. Dumont NA, Bentzinger CF, Sincennes MC, et al. Satellite cells and skeletal muscle regeneration. Compr Physiol. 2015;5:1027–1059. - PubMed
    1. Frangogiannis NG. Pathophysiology of myocardial infarction. Compr Physiol. 2015;5:1841–1875. - PubMed

    1. Duffield JS. Cellular and molecular mechanisms in kidney fibrosis. J Clin Investig. 2014;124:2299–2306. A highly informative and well-illustrated review on the cell biology of renal fibrosis

    1. Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis. Cell Mol Life Sci. 2014;71:549–574. - PMC - PubMed

LinkOut - more resources