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Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration

The caveolin-1 scaffolding domain (CSD, amino acids 82–101 of caveolin-1) has been shown to suppress bleomycin-induced lung and skin fibrosis and angiotensin II (AngII)-induced myocardial fibrosis. To identify active subregions within CSD, we split its sequence into three slightly overlapping 8-amin...

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Autores principales: Reese, Charles F., Chinnakkannu, Panneerselvam, Tourkina, Elena, Hoffman, Stanley, Kuppuswamy, Dhandapani
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880820/
https://www.ncbi.nlm.nih.gov/pubmed/35213624
http://dx.doi.org/10.1371/journal.pone.0264413
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author Reese, Charles F.
Chinnakkannu, Panneerselvam
Tourkina, Elena
Hoffman, Stanley
Kuppuswamy, Dhandapani
author_facet Reese, Charles F.
Chinnakkannu, Panneerselvam
Tourkina, Elena
Hoffman, Stanley
Kuppuswamy, Dhandapani
author_sort Reese, Charles F.
collection PubMed
description The caveolin-1 scaffolding domain (CSD, amino acids 82–101 of caveolin-1) has been shown to suppress bleomycin-induced lung and skin fibrosis and angiotensin II (AngII)-induced myocardial fibrosis. To identify active subregions within CSD, we split its sequence into three slightly overlapping 8-amino acid subregions (82–89, 88–95, and 94–101). Interestingly, all three peptides showed activity. In bleomycin-treated mice, all three subregions suppressed the pathological effects on lung and skin tissue morphology. In addition, while bone marrow monocytes isolated from bleomycin-treated mice showed greatly enhanced migration in vitro toward CXCL12, treatment in vivo with CSD and its subregions almost completely suppressed this enhanced migration. In AngII-induced heart failure, both 82–89 and 88–95 significantly suppressed fibrosis (both Col I and HSP47 levels), microvascular leakage, and heart weight/ body weight ratio (HW/BW) while improving ventricular function. In contrast, while 94–101 suppressed the increase in Col I, it did not improve the other parameters. The idea that all three subregions can be active depending on the assay was further supported by experiments studying the in vitro migration of human monocytes in which all three subregions were extremely active. These studies are very novel in that it has been suggested that there is only one active region within CSD that is centered on amino acids 90–92. In contrast, we demonstrate here the presence of other active regions within CSD.
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spelling pubmed-88808202022-02-26 Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration Reese, Charles F. Chinnakkannu, Panneerselvam Tourkina, Elena Hoffman, Stanley Kuppuswamy, Dhandapani PLoS One Research Article The caveolin-1 scaffolding domain (CSD, amino acids 82–101 of caveolin-1) has been shown to suppress bleomycin-induced lung and skin fibrosis and angiotensin II (AngII)-induced myocardial fibrosis. To identify active subregions within CSD, we split its sequence into three slightly overlapping 8-amino acid subregions (82–89, 88–95, and 94–101). Interestingly, all three peptides showed activity. In bleomycin-treated mice, all three subregions suppressed the pathological effects on lung and skin tissue morphology. In addition, while bone marrow monocytes isolated from bleomycin-treated mice showed greatly enhanced migration in vitro toward CXCL12, treatment in vivo with CSD and its subregions almost completely suppressed this enhanced migration. In AngII-induced heart failure, both 82–89 and 88–95 significantly suppressed fibrosis (both Col I and HSP47 levels), microvascular leakage, and heart weight/ body weight ratio (HW/BW) while improving ventricular function. In contrast, while 94–101 suppressed the increase in Col I, it did not improve the other parameters. The idea that all three subregions can be active depending on the assay was further supported by experiments studying the in vitro migration of human monocytes in which all three subregions were extremely active. These studies are very novel in that it has been suggested that there is only one active region within CSD that is centered on amino acids 90–92. In contrast, we demonstrate here the presence of other active regions within CSD. Public Library of Science 2022-02-25 /pmc/articles/PMC8880820/ /pubmed/35213624 http://dx.doi.org/10.1371/journal.pone.0264413 Text en © 2022 Reese et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Reese, Charles F.
Chinnakkannu, Panneerselvam
Tourkina, Elena
Hoffman, Stanley
Kuppuswamy, Dhandapani
Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration
title Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration
title_full Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration
title_fullStr Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration
title_full_unstemmed Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration
title_short Multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration
title_sort multiple subregions within the caveolin-1 scaffolding domain inhibit fibrosis, microvascular leakage, and monocyte migration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880820/
https://www.ncbi.nlm.nih.gov/pubmed/35213624
http://dx.doi.org/10.1371/journal.pone.0264413
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