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Anti-fibrotic effects of pharmacologic FGF-2: a review of recent literature

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Abstract

Fibrosis is a process of pathological tissue repair that replaces damaged, formerly functional tissue with a non-functional, collagen-rich scar. Complications of fibrotic pathologies, which can arise in numerous organs and from numerous conditions, result in nearly half of deaths in the developed world. Despite this, therapies that target fibrosis at its mechanistic roots are still notably lacking. The ubiquity of the occurrence of fibrosis in myriad organs emphasizes the fact that there are shared mechanisms underlying fibrotic conditions, which may serve as common therapeutic targets for multiple fibrotic diseases of varied organs. Thus, study of the basic science of fibrosis and of anti-fibrotic modalities is critical to therapeutic development and may have potential to translate across organs and disease states. Fibroblast growth factor 2 (FGF-2) is a broadly studied member of the fibroblast growth factors, a family of multipotent cytokines implicated in diverse cellular and tissue processes, which has previously been recognized for its anti-fibrotic potential. However, the mechanisms underlying this potential are not fully understood, nor is the potential for its use to ameliorate fibrosis in diverse pathologies and tissues. Presented here is a review of recent literature that sheds further light on these questions, with the hopes of inspiring further research into the mechanisms underlying the anti-fibrotic activities of FGF-2, as well as the disease conditions for which pharmacologic FGF-2 might be a useful option in the future.

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Abbreviations

FGF-2:

Fibroblast growth factor 2

FGFR:

Fibroblast growth factor receptor

IPF:

Idiopathic pulmonary fibrosis

MAPK:

Mitogen-activated protein kinase

STAT:

Signal transducer and activator of transcription

PLC:

Phospholipase C

HIF:

Hypoxia-inducible factor

VEGF:

Vascular endothelial growth factor

SVR:

Surgical ventricular restoration

TGF-β:

Transforming growth factor beta

LPS:

Lipopolysaccharide

PEGDA:

Polyethylene glycol diacrylate

MMP:

Matrix metalloproteinase

HGF:

Hepatocyte growth factor

CT:

Computed tomography

TCKO:

Triple conditional knockout

AEC2:

Alveolar type II epithelial cells

MEK:

MAPK/ERK Kinase

ERK:

Extracellular signal-regulated kinase

SRF:

Serum response factor

MRTF:

Myocardin-related transcription factor

PDGFR:

Platelet-derived growth factor

SPION:

Superparamagnetic iron oxide nanoparticle

α-SMA:

Smooth muscle alpha actin

NOD-SCID:

Non-obese diabetic severe combined immunodeficiency

rAAV:

Recombinant adeno-associated virus

ECM:

Extracellular matrix

YAP/TAZ:

Yes-associated protein/Transcriptional co-activator with PDZ-binding motif

LSE:

Living skin equivalent

TGF-βR:

Transforming growth factor beta receptor

PEG:

Polyethylene glycol

VIC:

Valvular interstitial cell

Elk-1:

ETS Like-1

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

BM-MSC:

Bone marrow-derived mesenchymal stem cell

ADAMTS:

A disintegrin and metalloproteinase with thrombospondin motifs

LOX:

Lysyl oxidase

CD:

Cluster of differentiation

CCN2:

Cellular communication network factor 2

CTGF:

Connective tissue growth factor

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Acknowledgements

I would like to thank the myriad researchers in the FGF community, across decades and continents, for their pivotal past, present, and future contributions to our understanding of FGF biology. Figures were made with Biorender.com.

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    David M. Dolivo

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Dolivo, D.M. Anti-fibrotic effects of pharmacologic FGF-2: a review of recent literature. J Mol Med 100, 847–860 (2022). https://doi.org/10.1007/s00109-022-02194-3

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