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Contribution of keratinocytes to dermal fibrosis

The cellular pathogenesis of fibrotic disorders including systemic sclerosis (SSc) remains largely speculative. Currently, the altered function of endothelial cells and fibroblasts under the influence of an inappropriate immune response are considered central pathogenic events in SSc. Adding to this...

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Autores principales: Russo, Barbara, Brembilla, Nicolò C., Chizzolini, Carlo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9594125/
https://www.ncbi.nlm.nih.gov/pubmed/35994728
http://dx.doi.org/10.1097/BOR.0000000000000895
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author Russo, Barbara
Brembilla, Nicolò C.
Chizzolini, Carlo
author_facet Russo, Barbara
Brembilla, Nicolò C.
Chizzolini, Carlo
author_sort Russo, Barbara
collection PubMed
description The cellular pathogenesis of fibrotic disorders including systemic sclerosis (SSc) remains largely speculative. Currently, the altered function of endothelial cells and fibroblasts under the influence of an inappropriate immune response are considered central pathogenic events in SSc. Adding to this complexity, novel evidence here reviewed suggests that keratinocytes may concur in the development of skin fibrosis. RECENT FINDINGS: Epidermal equivalents (EE) generated from primary SSc keratinocytes display a distinct gene expression program when compared to healthy donor (HD) EE. SSc-EE, among others, exhibited enhanced oxidative and metabolic response pathways. Immunohistochemical studies demonstrated similarities between SSc-EE and SSc epidermis including altered keratinocyte differentiation, enhanced expression of activation markers, and reduced rate of basal keratinocytes proliferation. SSc-EE supernatants more than HD-EE modified the inflammatory and extracellular matrix deposition/resorption program of dermal fibroblasts. Further evidence indicated that the relative lack rather than the excess of interleukin-25 in keratinocytes may contribute to enhanced dermal fibrotic changes. Overall, these data support keratinocyte-intrinsic SSc-related modifications. SUMMARY: Improved methods for engineering epidermal and skin equivalents are helping to address the question whether keratinocyte alterations in SSc are primary and capable to dysregulate dermal homeostasis or secondary following dermal fibrotic changes.
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spelling pubmed-95941252022-10-27 Contribution of keratinocytes to dermal fibrosis Russo, Barbara Brembilla, Nicolò C. Chizzolini, Carlo Curr Opin Rheumatol RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by Shervin Assassi The cellular pathogenesis of fibrotic disorders including systemic sclerosis (SSc) remains largely speculative. Currently, the altered function of endothelial cells and fibroblasts under the influence of an inappropriate immune response are considered central pathogenic events in SSc. Adding to this complexity, novel evidence here reviewed suggests that keratinocytes may concur in the development of skin fibrosis. RECENT FINDINGS: Epidermal equivalents (EE) generated from primary SSc keratinocytes display a distinct gene expression program when compared to healthy donor (HD) EE. SSc-EE, among others, exhibited enhanced oxidative and metabolic response pathways. Immunohistochemical studies demonstrated similarities between SSc-EE and SSc epidermis including altered keratinocyte differentiation, enhanced expression of activation markers, and reduced rate of basal keratinocytes proliferation. SSc-EE supernatants more than HD-EE modified the inflammatory and extracellular matrix deposition/resorption program of dermal fibroblasts. Further evidence indicated that the relative lack rather than the excess of interleukin-25 in keratinocytes may contribute to enhanced dermal fibrotic changes. Overall, these data support keratinocyte-intrinsic SSc-related modifications. SUMMARY: Improved methods for engineering epidermal and skin equivalents are helping to address the question whether keratinocyte alterations in SSc are primary and capable to dysregulate dermal homeostasis or secondary following dermal fibrotic changes. Lippincott Williams & Wilkins 2022-11 2022-08-16 /pmc/articles/PMC9594125/ /pubmed/35994728 http://dx.doi.org/10.1097/BOR.0000000000000895 Text en Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by Shervin Assassi
Russo, Barbara
Brembilla, Nicolò C.
Chizzolini, Carlo
Contribution of keratinocytes to dermal fibrosis
title Contribution of keratinocytes to dermal fibrosis
title_full Contribution of keratinocytes to dermal fibrosis
title_fullStr Contribution of keratinocytes to dermal fibrosis
title_full_unstemmed Contribution of keratinocytes to dermal fibrosis
title_short Contribution of keratinocytes to dermal fibrosis
title_sort contribution of keratinocytes to dermal fibrosis
topic RAYNAUD PHENOMENON, SCLERODERMA, OVERLAP SYNDROMES AND OTHER FIBROSING SYNDROMES: Edited by Shervin Assassi
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9594125/
https://www.ncbi.nlm.nih.gov/pubmed/35994728
http://dx.doi.org/10.1097/BOR.0000000000000895
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