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PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis

Systemic sclerosis (SSc) is a chronic, multisystem orphan disease with a highly variable clinical course, high mortality rate, and a poorly understood complex pathogenesis. We have identified an important role for a subpopulation of monocytes and macrophages characterized by surface expression of th...

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Autores principales: Xu, Dan, Bhattacharyya, Swati, Wang, Wenxia, Ifergan, Igal, Wong, Ming-Yi Alice Chiang, Procissi, Daniele, Yeldandi, Anjana, Bale, Swarna, Marangoni, Roberta Goncalves, Horbinski, Craig, Miller, Stephen D., Varga, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983146/
https://www.ncbi.nlm.nih.gov/pubmed/35104243
http://dx.doi.org/10.1172/jci.insight.151037
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author Xu, Dan
Bhattacharyya, Swati
Wang, Wenxia
Ifergan, Igal
Wong, Ming-Yi Alice Chiang
Procissi, Daniele
Yeldandi, Anjana
Bale, Swarna
Marangoni, Roberta Goncalves
Horbinski, Craig
Miller, Stephen D.
Varga, John
author_facet Xu, Dan
Bhattacharyya, Swati
Wang, Wenxia
Ifergan, Igal
Wong, Ming-Yi Alice Chiang
Procissi, Daniele
Yeldandi, Anjana
Bale, Swarna
Marangoni, Roberta Goncalves
Horbinski, Craig
Miller, Stephen D.
Varga, John
author_sort Xu, Dan
collection PubMed
description Systemic sclerosis (SSc) is a chronic, multisystem orphan disease with a highly variable clinical course, high mortality rate, and a poorly understood complex pathogenesis. We have identified an important role for a subpopulation of monocytes and macrophages characterized by surface expression of the scavenger receptor macrophage receptor with collagenous structure (MARCO) in chronic inflammation and fibrosis in SSc and in preclinical disease models. We show that MARCO(+) monocytes and macrophages accumulate in lesional skin and lung in topographic proximity to activated myofibroblasts in patients with SSc and in the bleomycin-induced mouse model of SSc. Short-term treatment of mice with a potentially novel nanoparticle, poly(lactic-co-glycolic) acid (PLG), which is composed of a carboxylated, FDA-approved, biodegradable polymer and modulates activation and trafficking of MARCO(+) inflammatory monocytes, markedly attenuated bleomycin-induced skin and lung inflammation and fibrosis. Mechanistically, in isolated cells in culture, PLG nanoparticles inhibited TGF-dependent fibrotic responses in vitro. Thus, MARCO(+) monocytes are potent effector cells of skin and lung fibrosis and can be therapeutically targeted in SSc using PLG nanoparticles.
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spelling pubmed-89831462022-04-07 PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis Xu, Dan Bhattacharyya, Swati Wang, Wenxia Ifergan, Igal Wong, Ming-Yi Alice Chiang Procissi, Daniele Yeldandi, Anjana Bale, Swarna Marangoni, Roberta Goncalves Horbinski, Craig Miller, Stephen D. Varga, John JCI Insight Research Article Systemic sclerosis (SSc) is a chronic, multisystem orphan disease with a highly variable clinical course, high mortality rate, and a poorly understood complex pathogenesis. We have identified an important role for a subpopulation of monocytes and macrophages characterized by surface expression of the scavenger receptor macrophage receptor with collagenous structure (MARCO) in chronic inflammation and fibrosis in SSc and in preclinical disease models. We show that MARCO(+) monocytes and macrophages accumulate in lesional skin and lung in topographic proximity to activated myofibroblasts in patients with SSc and in the bleomycin-induced mouse model of SSc. Short-term treatment of mice with a potentially novel nanoparticle, poly(lactic-co-glycolic) acid (PLG), which is composed of a carboxylated, FDA-approved, biodegradable polymer and modulates activation and trafficking of MARCO(+) inflammatory monocytes, markedly attenuated bleomycin-induced skin and lung inflammation and fibrosis. Mechanistically, in isolated cells in culture, PLG nanoparticles inhibited TGF-dependent fibrotic responses in vitro. Thus, MARCO(+) monocytes are potent effector cells of skin and lung fibrosis and can be therapeutically targeted in SSc using PLG nanoparticles. American Society for Clinical Investigation 2022-03-08 /pmc/articles/PMC8983146/ /pubmed/35104243 http://dx.doi.org/10.1172/jci.insight.151037 Text en © 2022 Xu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Xu, Dan
Bhattacharyya, Swati
Wang, Wenxia
Ifergan, Igal
Wong, Ming-Yi Alice Chiang
Procissi, Daniele
Yeldandi, Anjana
Bale, Swarna
Marangoni, Roberta Goncalves
Horbinski, Craig
Miller, Stephen D.
Varga, John
PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis
title PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis
title_full PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis
title_fullStr PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis
title_full_unstemmed PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis
title_short PLG nanoparticles target fibroblasts and MARCO(+) monocytes to reverse multiorgan fibrosis
title_sort plg nanoparticles target fibroblasts and marco(+) monocytes to reverse multiorgan fibrosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983146/
https://www.ncbi.nlm.nih.gov/pubmed/35104243
http://dx.doi.org/10.1172/jci.insight.151037
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