Introduction - Fibrosis is a pathophysiological response to injury characterized by excess, abnormal extracellular matrix (ECM) deposition disrupting the normal tissue architecture and function of affected organs. Lung fibrosis may occur as a component of systemic or local diseases, but the most pernicious clinical form is idiopathic pulmonary fibrosis (IPF), which represents a major challenge for pneumologists, being refractory to any conventional therapy. This has prompted the development of suitable animal models of lung fibrosis to test novel therapies. Objectives – This minireview summarizes the current knowledge on the anti-fibrotic properties of relaxin, a natural hormone capable of modulating ECM turn-over in multiple target organs, which can be viewed as a promising anti-fibrotic drug. In fact, human recombinant relaxin has been and is currently being investigated in clinical trials due to its favourable bioactivity profile. Results and Conclusion – Based on several in vitro and in vivo studies, relaxin has emerged as a key endogenous factor involved in the regulation of ECM synthesis and remodelling by fibroblasts. Knock-out mice for relaxin or its receptor are prone to heart, kidney and lung fibrosis: in the former animal model, the pro-fibrotic trend can be reverted by exogenous administration of the hormone, implicating its therapeutic potential. To overcome the intrinsic limitations of the peptide properties of the hormone, low molecular weight relaxin receptor agonists have been synthesised and are currently being evaluated as alternative treatments. As shown using a mouse model of bleomycin-induced lung fibrosis, these compounds are capable of blunting the pulmonary inflammatory reaction to bleomycin and the subsequent enhanced collagen deposition. Taken together, these existing notions and clues suggest that relaxin and related molecules deserve to be further investigated as possible anti-fibrotic drugs.

New views on relaxin and relaxin-receptor agonists for the treatment of lung fibrosis. evidences from in vivo models / A.Pini; R.Shemesh; C.S.Samuel; D.Bani. - In: THE ANNALS OF RESPIRATORY MEDICINE. - ISSN 2042-4701. - ELETTRONICO. - 2 (2):(2011), pp. 1-10.

New views on relaxin and relaxin-receptor agonists for the treatment of lung fibrosis. evidences from in vivo models

PINI, ALESSANDRO;BANI, DANIELE
2011

Abstract

Introduction - Fibrosis is a pathophysiological response to injury characterized by excess, abnormal extracellular matrix (ECM) deposition disrupting the normal tissue architecture and function of affected organs. Lung fibrosis may occur as a component of systemic or local diseases, but the most pernicious clinical form is idiopathic pulmonary fibrosis (IPF), which represents a major challenge for pneumologists, being refractory to any conventional therapy. This has prompted the development of suitable animal models of lung fibrosis to test novel therapies. Objectives – This minireview summarizes the current knowledge on the anti-fibrotic properties of relaxin, a natural hormone capable of modulating ECM turn-over in multiple target organs, which can be viewed as a promising anti-fibrotic drug. In fact, human recombinant relaxin has been and is currently being investigated in clinical trials due to its favourable bioactivity profile. Results and Conclusion – Based on several in vitro and in vivo studies, relaxin has emerged as a key endogenous factor involved in the regulation of ECM synthesis and remodelling by fibroblasts. Knock-out mice for relaxin or its receptor are prone to heart, kidney and lung fibrosis: in the former animal model, the pro-fibrotic trend can be reverted by exogenous administration of the hormone, implicating its therapeutic potential. To overcome the intrinsic limitations of the peptide properties of the hormone, low molecular weight relaxin receptor agonists have been synthesised and are currently being evaluated as alternative treatments. As shown using a mouse model of bleomycin-induced lung fibrosis, these compounds are capable of blunting the pulmonary inflammatory reaction to bleomycin and the subsequent enhanced collagen deposition. Taken together, these existing notions and clues suggest that relaxin and related molecules deserve to be further investigated as possible anti-fibrotic drugs.
2011
2 (2)
1
10
A.Pini; R.Shemesh; C.S.Samuel; D.Bani
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/426299
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