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Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis

Glycoprotein nonmetastatic melanoma protein B (GPNMB) is involved in various cell functions such as cell adhesion, migration, proliferation, and differentiation. In this study, we set forth to determine the role of GPNMB in systemic sclerosis (SSc) fibroblasts. Dermal fibroblasts were isolated from...

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Autores principales: Palisoc, Pamela J., Vaikutis, Leah, Gurrea-Rubio, Mikel, Model, Ellen N., O’mara, Morgan M., Ory, Sarah, Vichaikul, Sirapa, Khanna, Dinesh, Tsou, Pei-Suen, Sawalha, Amr H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907428/
https://www.ncbi.nlm.nih.gov/pubmed/35280996
http://dx.doi.org/10.3389/fimmu.2022.814533
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author Palisoc, Pamela J.
Vaikutis, Leah
Gurrea-Rubio, Mikel
Model, Ellen N.
O’mara, Morgan M.
Ory, Sarah
Vichaikul, Sirapa
Khanna, Dinesh
Tsou, Pei-Suen
Sawalha, Amr H.
author_facet Palisoc, Pamela J.
Vaikutis, Leah
Gurrea-Rubio, Mikel
Model, Ellen N.
O’mara, Morgan M.
Ory, Sarah
Vichaikul, Sirapa
Khanna, Dinesh
Tsou, Pei-Suen
Sawalha, Amr H.
author_sort Palisoc, Pamela J.
collection PubMed
description Glycoprotein nonmetastatic melanoma protein B (GPNMB) is involved in various cell functions such as cell adhesion, migration, proliferation, and differentiation. In this study, we set forth to determine the role of GPNMB in systemic sclerosis (SSc) fibroblasts. Dermal fibroblasts were isolated from skin biopsies from healthy subjects and patients with diffuse cutaneous (dc)SSc. GPNMB was upregulated in dcSSc fibroblasts compared to normal fibroblasts, and correlated negatively with the modified Rodnan skin score. In addition, dcSSc fibroblasts secreted higher levels of soluble (s)GPNMB (147.4 ± 50.2 pg/ml vs. 84.8 ± 14.8 pg/ml, p<0.05), partly due to increased ADAM10. sGPNMB downregulated profibrotic genes in dcSSc fibroblasts and inhibited cell proliferation and gel contraction. The anti-fibrotic effect of sGPNMB was at least in part mediated through CD44, which is regulated by histone acetylation. TGFβ downregulated GPNMB and decreased the release of its soluble form in normal fibroblasts. In dcSSc fibroblasts, GPNMB is upregulated by its own soluble form. Our data demonstrate an anti-fibrotic role of sGPNMB in SSc and established a role for the ADAM10-sGPNMB-CD44 axis in dermal fibroblasts. Upregulating GPNMB expression might provide a novel therapeutic approach in SSc.
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spelling pubmed-89074282022-03-11 Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis Palisoc, Pamela J. Vaikutis, Leah Gurrea-Rubio, Mikel Model, Ellen N. O’mara, Morgan M. Ory, Sarah Vichaikul, Sirapa Khanna, Dinesh Tsou, Pei-Suen Sawalha, Amr H. Front Immunol Immunology Glycoprotein nonmetastatic melanoma protein B (GPNMB) is involved in various cell functions such as cell adhesion, migration, proliferation, and differentiation. In this study, we set forth to determine the role of GPNMB in systemic sclerosis (SSc) fibroblasts. Dermal fibroblasts were isolated from skin biopsies from healthy subjects and patients with diffuse cutaneous (dc)SSc. GPNMB was upregulated in dcSSc fibroblasts compared to normal fibroblasts, and correlated negatively with the modified Rodnan skin score. In addition, dcSSc fibroblasts secreted higher levels of soluble (s)GPNMB (147.4 ± 50.2 pg/ml vs. 84.8 ± 14.8 pg/ml, p<0.05), partly due to increased ADAM10. sGPNMB downregulated profibrotic genes in dcSSc fibroblasts and inhibited cell proliferation and gel contraction. The anti-fibrotic effect of sGPNMB was at least in part mediated through CD44, which is regulated by histone acetylation. TGFβ downregulated GPNMB and decreased the release of its soluble form in normal fibroblasts. In dcSSc fibroblasts, GPNMB is upregulated by its own soluble form. Our data demonstrate an anti-fibrotic role of sGPNMB in SSc and established a role for the ADAM10-sGPNMB-CD44 axis in dermal fibroblasts. Upregulating GPNMB expression might provide a novel therapeutic approach in SSc. Frontiers Media S.A. 2022-02-24 /pmc/articles/PMC8907428/ /pubmed/35280996 http://dx.doi.org/10.3389/fimmu.2022.814533 Text en Copyright © 2022 Palisoc, Vaikutis, Gurrea-Rubio, Model, O’mara, Ory, Vichaikul, Khanna, Tsou and Sawalha https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Palisoc, Pamela J.
Vaikutis, Leah
Gurrea-Rubio, Mikel
Model, Ellen N.
O’mara, Morgan M.
Ory, Sarah
Vichaikul, Sirapa
Khanna, Dinesh
Tsou, Pei-Suen
Sawalha, Amr H.
Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis
title Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis
title_full Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis
title_fullStr Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis
title_full_unstemmed Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis
title_short Functional Characterization of Glycoprotein Nonmetastatic Melanoma Protein B in Scleroderma Fibrosis
title_sort functional characterization of glycoprotein nonmetastatic melanoma protein b in scleroderma fibrosis
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8907428/
https://www.ncbi.nlm.nih.gov/pubmed/35280996
http://dx.doi.org/10.3389/fimmu.2022.814533
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