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Serotonin and Fibrosis

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5-HT2B Receptors

Part of the book series: The Receptors ((REC,volume 35))

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Abstract

Fibrosis can occur in many tissues within the body, including skin, liver, lung, heart, intestine and pancreas. The wound healing response that replaces damaged tissue with non-functional collagen-rich scar tissue to maintain the physical boundaries of the affected organ, 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. A ubiquitous characteristic of fibrosis is the presence of myofibroblasts, a contractile cell that deposits high amounts of fibrotic extracellular matrix including type I collagen and extra-domain A isoform of fibronectin. Disturbances in the regulation of these processes can result in a wide range of pathological conditions, which are associated with tissue fibrosis, from excessive scarring to systemic sclerosis. Clinical evidences exist suggesting a role for serotonin and serotonin agonists in fibrosis. The pro-fibrotic activity of serotonin in vivo is due at least in part to its direct effect on fibroblasts and/or myofibroblast progenitors, TGF-β serotonergic responses. Distinct serotonin receptors are involved in the fibrotic pathophysiology that is mainly mediated through signaling via 5-HT2A and 5-HT2B receptors. Pharmaceutical inhibition of these specific serotonin receptors may be beneficial for the treatment of fibrotic disorders.

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Abbreviations

COL1A1:

Collagen 1α1

COL1A2:

Collagen 1α2

CTGF:

Connective tissue growth factor

ECM:

Extracellular matrix

FN1:

Fibronectin

MDMA-“Ecstasy”:

3,4-methylenedioxy-methamphetamine

SMA:

Smooth muscle actin

SSRI/SNRI:

Serotonin norepinephrine re-uptake inhibitors

SERT/5-HTT:

Serotonin transporter SLC6A4

αSMA:

Alpha smooth muscle actin

SSc:

Systemic sclerosis

TGF-β:

Transforming growth factor beta

TPH1:

Tryptophan hydroxylase

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Authors and Affiliations

  1. Department of Rheumatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland

    Oliver Distler, Michel Neidhart & Przemysław Błyszczuk

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  1. Oliver Distler
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  2. Michel Neidhart
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  3. Przemysław Błyszczuk
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Correspondence to Oliver Distler .

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Editors and Affiliations

  1. Inserm, U1270, Institut du Fer a Moulin, Paris, France

    Luc Maroteaux

  2. Pharmacology, Strasbourg Medical school, Strasbourg, France

    Laurent Monassier

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Distler, O., Neidhart, M., Błyszczuk, P. (2021). Serotonin and Fibrosis. In: Maroteaux, L., Monassier, L. (eds) 5-HT2B Receptors. The Receptors, vol 35. Springer, Cham. https://doi.org/10.1007/978-3-030-55920-5_13

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