Anti-fibrotic mechanisms of angiotensin AT2 -receptor stimulation

Colin Sumners, A Augusto Peluso, Andreas Houe Hausgaard, Jesper Bork Bertelsen, U Muscha Steckelings

Publikation: Bidrag til tidsskriftReviewForskningpeer review

Resumé

The angiotensin AT2 -receptor is a main receptor of the protective arm of the renin-angiotensin-system. Understanding of this unconventional G-protein coupled receptor has significantly advanced during the past decade, largely because of the availability of a selective non-peptide AT2 -receptor agonist, which allowed the conduct of a multitude of studies in animal disease models. This article reviews such preclinical studies that in their entirety provide strong evidence for an anti-fibrotic effect mediated by activation of the AT2 -receptor. Prevention of the development of fibrosis by AT2 -receptor stimulation has been demonstrated in lung, heart, blood vessels, kidney, pancreas and skin. In lung, AT2 -receptor stimulation was even able to reverse existing fibrosis. The article further discusses intracellular signalling mechanisms mediating the AT2 -receptor coupled anti-fibrotic effect, including activation of phosphatases and subsequent interference with pro-fibrotic signalling pathways, induction of matrix-metalloproteinases, and hetero-dimerisation with the AT1 -receptor, the TGF-βRII-receptor or the RXFP1-receptor for relaxin. Knowledge of the anti-fibrotic effects of the AT2 -receptor is of particular relevance, because drugs targeting this receptor have entered clinical development for indications involving fibrotic diseases. This article is protected by copyright. All rights reserved.

OriginalsprogEngelsk
Artikelnummere13280
TidsskriftActa Physiologica
Vol/bind227
Udgave nummer1
Antal sider16
ISSN1748-1708
DOI
StatusUdgivet - sep. 2019

Fingeraftryk

Angiotensin Type 2 Receptor
Drug Receptors
Lung
Dimerization
Renin-Angiotensin System
G-Protein-Coupled Receptors
Matrix Metalloproteinases
Phosphoric Monoester Hydrolases
Pancreas
Kidney
Skin
relaxin receptors

Citer dette

Sumners, C., Peluso, A. A., Houe Hausgaard, A., Bork Bertelsen, J., & Steckelings, U. M. (2019). Anti-fibrotic mechanisms of angiotensin AT2 -receptor stimulation. Acta Physiologica, 227(1), [e13280]. https://doi.org/10.1111/apha.13280
Sumners, Colin ; Peluso, A Augusto ; Houe Hausgaard, Andreas ; Bork Bertelsen, Jesper ; Steckelings, U Muscha. / Anti-fibrotic mechanisms of angiotensin AT2 -receptor stimulation. I: Acta Physiologica. 2019 ; Bind 227, Nr. 1.
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abstract = "The angiotensin AT2 -receptor is a main receptor of the protective arm of the renin-angiotensin-system. Understanding of this unconventional G-protein coupled receptor has significantly advanced during the past decade, largely because of the availability of a selective non-peptide AT2 -receptor agonist, which allowed the conduct of a multitude of studies in animal disease models. This article reviews such preclinical studies that in their entirety provide strong evidence for an anti-fibrotic effect mediated by activation of the AT2 -receptor. Prevention of the development of fibrosis by AT2 -receptor stimulation has been demonstrated in lung, heart, blood vessels, kidney, pancreas and skin. In lung, AT2 -receptor stimulation was even able to reverse existing fibrosis. The article further discusses intracellular signalling mechanisms mediating the AT2 -receptor coupled anti-fibrotic effect, including activation of phosphatases and subsequent interference with pro-fibrotic signalling pathways, induction of matrix-metalloproteinases, and hetero-dimerisation with the AT1 -receptor, the TGF-βRII-receptor or the RXFP1-receptor for relaxin. Knowledge of the anti-fibrotic effects of the AT2 -receptor is of particular relevance, because drugs targeting this receptor have entered clinical development for indications involving fibrotic diseases. This article is protected by copyright. All rights reserved.",
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author = "Colin Sumners and Peluso, {A Augusto} and {Houe Hausgaard}, Andreas and {Bork Bertelsen}, Jesper and Steckelings, {U Muscha}",
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Sumners, C, Peluso, AA, Houe Hausgaard, A, Bork Bertelsen, J & Steckelings, UM 2019, 'Anti-fibrotic mechanisms of angiotensin AT2 -receptor stimulation', Acta Physiologica, bind 227, nr. 1, e13280. https://doi.org/10.1111/apha.13280

Anti-fibrotic mechanisms of angiotensin AT2 -receptor stimulation. / Sumners, Colin; Peluso, A Augusto; Houe Hausgaard, Andreas; Bork Bertelsen, Jesper; Steckelings, U Muscha.

I: Acta Physiologica, Bind 227, Nr. 1, e13280, 09.2019.

Publikation: Bidrag til tidsskriftReviewForskningpeer review

TY - JOUR

T1 - Anti-fibrotic mechanisms of angiotensin AT2 -receptor stimulation

AU - Sumners, Colin

AU - Peluso, A Augusto

AU - Houe Hausgaard, Andreas

AU - Bork Bertelsen, Jesper

AU - Steckelings, U Muscha

PY - 2019/9

Y1 - 2019/9

N2 - The angiotensin AT2 -receptor is a main receptor of the protective arm of the renin-angiotensin-system. Understanding of this unconventional G-protein coupled receptor has significantly advanced during the past decade, largely because of the availability of a selective non-peptide AT2 -receptor agonist, which allowed the conduct of a multitude of studies in animal disease models. This article reviews such preclinical studies that in their entirety provide strong evidence for an anti-fibrotic effect mediated by activation of the AT2 -receptor. Prevention of the development of fibrosis by AT2 -receptor stimulation has been demonstrated in lung, heart, blood vessels, kidney, pancreas and skin. In lung, AT2 -receptor stimulation was even able to reverse existing fibrosis. The article further discusses intracellular signalling mechanisms mediating the AT2 -receptor coupled anti-fibrotic effect, including activation of phosphatases and subsequent interference with pro-fibrotic signalling pathways, induction of matrix-metalloproteinases, and hetero-dimerisation with the AT1 -receptor, the TGF-βRII-receptor or the RXFP1-receptor for relaxin. Knowledge of the anti-fibrotic effects of the AT2 -receptor is of particular relevance, because drugs targeting this receptor have entered clinical development for indications involving fibrotic diseases. This article is protected by copyright. All rights reserved.

AB - The angiotensin AT2 -receptor is a main receptor of the protective arm of the renin-angiotensin-system. Understanding of this unconventional G-protein coupled receptor has significantly advanced during the past decade, largely because of the availability of a selective non-peptide AT2 -receptor agonist, which allowed the conduct of a multitude of studies in animal disease models. This article reviews such preclinical studies that in their entirety provide strong evidence for an anti-fibrotic effect mediated by activation of the AT2 -receptor. Prevention of the development of fibrosis by AT2 -receptor stimulation has been demonstrated in lung, heart, blood vessels, kidney, pancreas and skin. In lung, AT2 -receptor stimulation was even able to reverse existing fibrosis. The article further discusses intracellular signalling mechanisms mediating the AT2 -receptor coupled anti-fibrotic effect, including activation of phosphatases and subsequent interference with pro-fibrotic signalling pathways, induction of matrix-metalloproteinases, and hetero-dimerisation with the AT1 -receptor, the TGF-βRII-receptor or the RXFP1-receptor for relaxin. Knowledge of the anti-fibrotic effects of the AT2 -receptor is of particular relevance, because drugs targeting this receptor have entered clinical development for indications involving fibrotic diseases. This article is protected by copyright. All rights reserved.

KW - angiotensin

KW - angiotensin AT -receptor

KW - fibrosis

KW - fibrotic disease

U2 - 10.1111/apha.13280

DO - 10.1111/apha.13280

M3 - Review

C2 - 30957953

VL - 227

JO - Acta Physiologica (Print)

JF - Acta Physiologica (Print)

SN - 1748-1708

IS - 1

M1 - e13280

ER -