SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib

Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by an excessive production and accumulation of collagen in the skin and internal organs often associated with interstitial lung disease (ILD). Its pathogenetic mechanisms are unknown and the lack of animal models mimicking the...

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Autores principales:	Francesca Ravanetti, Erica Ferrini, Luisa Ragionieri, Zahra Khalajzeyqami, Maria Nicastro, Yanto Ridwan, Alex Kleinjan, Gino Villetti, Andrea Grandi, Franco Fabio Stellari
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c97189aa45ba426ca1dc74f514bdf894
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spelling	oai:doaj.org-article:c97189aa45ba426ca1dc74f514bdf8942021-12-02T18:50:52ZSSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib10.1038/s41598-021-97728-z2045-2322https://doaj.org/article/c97189aa45ba426ca1dc74f514bdf8942021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97728-zhttps://doaj.org/toc/2045-2322Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by an excessive production and accumulation of collagen in the skin and internal organs often associated with interstitial lung disease (ILD). Its pathogenetic mechanisms are unknown and the lack of animal models mimicking the features of the human disease is creating a gap between the selection of anti-fibrotic drug candidates and effective therapies. In this work, we intended to pharmacologically validate a SSc-ILD model based on 1 week infusion of bleomycin (BLM) by osmotic minipumps in C57/BL6 mice, since it will serve as a tool for secondary drug screening. Nintedanib (NINT) has been used as a reference compound to investigate antifibrotic activity either for lung or skin fibrosis. Longitudinal Micro-CT analysis highlighted a significant slowdown in lung fibrosis progression after NINT treatment, which was confirmed by histology. However, no significant effect was observed on lung hydroxyproline content, inflammatory infiltrate and skin lipoatrophy. The modest pharmacological effect reported here could reflect the clinical outcome, highlighting the reliability of this model to better profile potential clinical drug candidates. The integrative approach presented herein, which combines longitudinal assessments with endpoint analyses, could be harnessed in drug discovery to generate more reliable, reproducible and robust readouts.Francesca RavanettiErica FerriniLuisa RagionieriZahra KhalajzeyqamiMaria NicastroYanto RidwanAlex KleinjanGino VillettiAndrea GrandiFranco Fabio StellariNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Francesca Ravanetti Erica Ferrini Luisa Ragionieri Zahra Khalajzeyqami Maria Nicastro Yanto Ridwan Alex Kleinjan Gino Villetti Andrea Grandi Franco Fabio Stellari SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib
description	Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by an excessive production and accumulation of collagen in the skin and internal organs often associated with interstitial lung disease (ILD). Its pathogenetic mechanisms are unknown and the lack of animal models mimicking the features of the human disease is creating a gap between the selection of anti-fibrotic drug candidates and effective therapies. In this work, we intended to pharmacologically validate a SSc-ILD model based on 1 week infusion of bleomycin (BLM) by osmotic minipumps in C57/BL6 mice, since it will serve as a tool for secondary drug screening. Nintedanib (NINT) has been used as a reference compound to investigate antifibrotic activity either for lung or skin fibrosis. Longitudinal Micro-CT analysis highlighted a significant slowdown in lung fibrosis progression after NINT treatment, which was confirmed by histology. However, no significant effect was observed on lung hydroxyproline content, inflammatory infiltrate and skin lipoatrophy. The modest pharmacological effect reported here could reflect the clinical outcome, highlighting the reliability of this model to better profile potential clinical drug candidates. The integrative approach presented herein, which combines longitudinal assessments with endpoint analyses, could be harnessed in drug discovery to generate more reliable, reproducible and robust readouts.
format	article
author	Francesca Ravanetti Erica Ferrini Luisa Ragionieri Zahra Khalajzeyqami Maria Nicastro Yanto Ridwan Alex Kleinjan Gino Villetti Andrea Grandi Franco Fabio Stellari
author_facet	Francesca Ravanetti Erica Ferrini Luisa Ragionieri Zahra Khalajzeyqami Maria Nicastro Yanto Ridwan Alex Kleinjan Gino Villetti Andrea Grandi Franco Fabio Stellari
author_sort	Francesca Ravanetti
title	SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib
title_short	SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib
title_full	SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib
title_fullStr	SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib
title_full_unstemmed	SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib
title_sort	ssc-ild mouse model induced by osmotic minipump delivered bleomycin: effect of nintedanib
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c97189aa45ba426ca1dc74f514bdf894
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SSC-ILD mouse model induced by osmotic minipump delivered bleomycin: effect of Nintedanib

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