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Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures

Functional tissue repair after injury or disease is governed by the regenerative or fibrotic response by cells within the tissue. In the case of corneal damage, keratocytes are a key cell type that determine the outcome of the remodeling response by either adapting to a fibroblast or myofibroblast p...

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Autores principales: van der Putten, Cas, van den Broek, Daniëlle, Kurniawan, Nicholas A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355510/
https://www.ncbi.nlm.nih.gov/pubmed/35938166
http://dx.doi.org/10.3389/fcell.2022.930373
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author van der Putten, Cas
van den Broek, Daniëlle
Kurniawan, Nicholas A.
author_facet van der Putten, Cas
van den Broek, Daniëlle
Kurniawan, Nicholas A.
author_sort van der Putten, Cas
collection PubMed
description Functional tissue repair after injury or disease is governed by the regenerative or fibrotic response by cells within the tissue. In the case of corneal damage, keratocytes are a key cell type that determine the outcome of the remodeling response by either adapting to a fibroblast or myofibroblast phenotype. Although a growing body of literature indicates that geometrical cues in the environment can influence Myo(fibroblast) phenotype, there is a lack of knowledge on whether and how differentiated keratocyte phenotype is affected by the curved tissue geometry in the cornea. To address this gap, in this study we characterized the phenotype of fibroblastic and transforming growth factor β (TGFβ)-induced myofibroblastic keratocytes and studied their migration behavior on curved culture substrates with varying curvatures. Immunofluorescence staining and quantification of cell morphological parameters showed that, generally, fibroblastic keratocytes were more likely to elongate, whereas myofibroblastic keratocytes expressed more pronounced α smooth muscle actin (α-SMA) and actin stress fibers as well as more mature focal adhesions. Interestingly, keratocyte adhesion on convex structures was weak and unstable, whereas they adhered normally on flat and concave structures. On concave cylinders, fibroblastic keratocytes migrated faster and with higher persistence along the longitudinal direction compared to myofibroblastic keratocytes. Moreover, this behavior became more pronounced on smaller cylinders (i.e., higher curvatures). Taken together, both keratocyte phenotypes can sense and respond to the sign and magnitude of substrate curvatures, however, myofibroblastic keratocytes exhibit weaker curvature sensing and slower migration on curved substrates compared to fibroblastic keratocytes. These findings provide fundamental insights into keratocyte phenotype after injury, but also exemplify the potential of tuning the physical cell environments in tissue engineering settings to steer towards a favorable regeneration response.
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spelling pubmed-93555102022-08-06 Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures van der Putten, Cas van den Broek, Daniëlle Kurniawan, Nicholas A. Front Cell Dev Biol Cell and Developmental Biology Functional tissue repair after injury or disease is governed by the regenerative or fibrotic response by cells within the tissue. In the case of corneal damage, keratocytes are a key cell type that determine the outcome of the remodeling response by either adapting to a fibroblast or myofibroblast phenotype. Although a growing body of literature indicates that geometrical cues in the environment can influence Myo(fibroblast) phenotype, there is a lack of knowledge on whether and how differentiated keratocyte phenotype is affected by the curved tissue geometry in the cornea. To address this gap, in this study we characterized the phenotype of fibroblastic and transforming growth factor β (TGFβ)-induced myofibroblastic keratocytes and studied their migration behavior on curved culture substrates with varying curvatures. Immunofluorescence staining and quantification of cell morphological parameters showed that, generally, fibroblastic keratocytes were more likely to elongate, whereas myofibroblastic keratocytes expressed more pronounced α smooth muscle actin (α-SMA) and actin stress fibers as well as more mature focal adhesions. Interestingly, keratocyte adhesion on convex structures was weak and unstable, whereas they adhered normally on flat and concave structures. On concave cylinders, fibroblastic keratocytes migrated faster and with higher persistence along the longitudinal direction compared to myofibroblastic keratocytes. Moreover, this behavior became more pronounced on smaller cylinders (i.e., higher curvatures). Taken together, both keratocyte phenotypes can sense and respond to the sign and magnitude of substrate curvatures, however, myofibroblastic keratocytes exhibit weaker curvature sensing and slower migration on curved substrates compared to fibroblastic keratocytes. These findings provide fundamental insights into keratocyte phenotype after injury, but also exemplify the potential of tuning the physical cell environments in tissue engineering settings to steer towards a favorable regeneration response. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9355510/ /pubmed/35938166 http://dx.doi.org/10.3389/fcell.2022.930373 Text en Copyright © 2022 van der Putten, van den Broek and Kurniawan. 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 Cell and Developmental Biology
van der Putten, Cas
van den Broek, Daniëlle
Kurniawan, Nicholas A.
Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures
title Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures
title_full Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures
title_fullStr Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures
title_full_unstemmed Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures
title_short Myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures
title_sort myofibroblast transdifferentiation of keratocytes results in slower migration and lower sensitivity to mesoscale curvatures
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355510/
https://www.ncbi.nlm.nih.gov/pubmed/35938166
http://dx.doi.org/10.3389/fcell.2022.930373
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