Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.

Dupuytren's disease (DD) is a fibroproliferative disorder of the palmar aponeurosis, which is characterized by a compound myofibrogenesis and evidenced by an increased expression of α-smooth muscle actin (α-SMA). In Dupuytren's tissue, higher levels of reactive oxygen species (ROS) are doc...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Carina Jaekel, Simon Thelen, Lisa Oezel, Marie H Wohltmann, Julia Wille, Joachim Windolf, Vera Grotheer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a00704b0bbec42be8f7be7e730088189
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a00704b0bbec42be8f7be7e730088189
record_format	dspace
spelling	oai:doaj.org-article:a00704b0bbec42be8f7be7e7300881892021-12-02T20:06:55ZIlluminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.1932-620310.1371/journal.pone.0253777https://doaj.org/article/a00704b0bbec42be8f7be7e7300881892021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253777https://doaj.org/toc/1932-6203Dupuytren's disease (DD) is a fibroproliferative disorder of the palmar aponeurosis, which is characterized by a compound myofibrogenesis and evidenced by an increased expression of α-smooth muscle actin (α-SMA). In Dupuytren's tissue, higher levels of reactive oxygen species (ROS) are documented, stimulating the proliferation and differentiation of myofibroblasts. Our preliminary study demonstrates that α-SMA-expression is significantly inhibited by blue light irradiation in DD. The objective of this study was to investigate the beneficial effect of blue light irradiation and to elucidate the influence of ROS on myofibrogenesis in the pathogenesis of DD. Therefore, an in-vitro model of human DD fibroblasts was used. DD fibroblasts and control fibroblasts isolated from carpal tunnel syndrome (CTS) were daily irradiated with 40 J/cm2 (λ = 453 nm, 38 mW/cm2). Protein expression of ROS-modulating enzymes (Catalase, NOX4, SOD1, MnSOD) and α-SMA were determined, and additionally analysed after a pharmacological inhibition of the TGF-β1-signaling with SB431542. Furthermore, the protein expression of α-SMA as surrogate parameter for myofibrogenesis was evaluated after applying different concentrations of long-lasting ROS. It could be determined that the beneficial blue light irradiation, which inhibited myofibrogenesis, is mediated by a significant inhibition of catalase protein expression. This effect should be accompanied with an increased intracellular ROS level. Proof of evidence was an H2O2-application on DD fibroblasts, also leading to a decreased myofibrogenesis. Furthermore, it could be demonstrated that endogenous MnSOD was significantly downregulated in resting DD fibroblasts. If DD fibroblasts were treated with the pharmacological inhibitor SB431542, myofibrogenesis was inhibited, but MnSOD expression was simultaneously elevated, which ought to affect ROS level by raising intracellular H2O2 amount. Blue light irradiation as well as the pharmacological action of SB431542 in consequence mediates their beneficial effect on disturbed myofibrogenesis in DD by further increasing ROS level. The present study demonstrates the importance of intracellular ROS homeostasis in DD and illuminates the beneficial effect of blue light as a promising therapy option for DD.Carina JaekelSimon ThelenLisa OezelMarie H WohltmannJulia WilleJoachim WindolfVera GrotheerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253777 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Carina Jaekel Simon Thelen Lisa Oezel Marie H Wohltmann Julia Wille Joachim Windolf Vera Grotheer Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.
description	Dupuytren's disease (DD) is a fibroproliferative disorder of the palmar aponeurosis, which is characterized by a compound myofibrogenesis and evidenced by an increased expression of α-smooth muscle actin (α-SMA). In Dupuytren's tissue, higher levels of reactive oxygen species (ROS) are documented, stimulating the proliferation and differentiation of myofibroblasts. Our preliminary study demonstrates that α-SMA-expression is significantly inhibited by blue light irradiation in DD. The objective of this study was to investigate the beneficial effect of blue light irradiation and to elucidate the influence of ROS on myofibrogenesis in the pathogenesis of DD. Therefore, an in-vitro model of human DD fibroblasts was used. DD fibroblasts and control fibroblasts isolated from carpal tunnel syndrome (CTS) were daily irradiated with 40 J/cm2 (λ = 453 nm, 38 mW/cm2). Protein expression of ROS-modulating enzymes (Catalase, NOX4, SOD1, MnSOD) and α-SMA were determined, and additionally analysed after a pharmacological inhibition of the TGF-β1-signaling with SB431542. Furthermore, the protein expression of α-SMA as surrogate parameter for myofibrogenesis was evaluated after applying different concentrations of long-lasting ROS. It could be determined that the beneficial blue light irradiation, which inhibited myofibrogenesis, is mediated by a significant inhibition of catalase protein expression. This effect should be accompanied with an increased intracellular ROS level. Proof of evidence was an H2O2-application on DD fibroblasts, also leading to a decreased myofibrogenesis. Furthermore, it could be demonstrated that endogenous MnSOD was significantly downregulated in resting DD fibroblasts. If DD fibroblasts were treated with the pharmacological inhibitor SB431542, myofibrogenesis was inhibited, but MnSOD expression was simultaneously elevated, which ought to affect ROS level by raising intracellular H2O2 amount. Blue light irradiation as well as the pharmacological action of SB431542 in consequence mediates their beneficial effect on disturbed myofibrogenesis in DD by further increasing ROS level. The present study demonstrates the importance of intracellular ROS homeostasis in DD and illuminates the beneficial effect of blue light as a promising therapy option for DD.
format	article
author	Carina Jaekel Simon Thelen Lisa Oezel Marie H Wohltmann Julia Wille Joachim Windolf Vera Grotheer
author_facet	Carina Jaekel Simon Thelen Lisa Oezel Marie H Wohltmann Julia Wille Joachim Windolf Vera Grotheer
author_sort	Carina Jaekel
title	Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.
title_short	Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.
title_full	Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.
title_fullStr	Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.
title_full_unstemmed	Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.
title_sort	illuminating the effect of beneficial blue light and ros-modulating enzymes in dupuytren's disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/a00704b0bbec42be8f7be7e730088189
work_keys_str_mv	AT carinajaekel illuminatingtheeffectofbeneficialbluelightandrosmodulatingenzymesindupuytrensdisease AT simonthelen illuminatingtheeffectofbeneficialbluelightandrosmodulatingenzymesindupuytrensdisease AT lisaoezel illuminatingtheeffectofbeneficialbluelightandrosmodulatingenzymesindupuytrensdisease AT mariehwohltmann illuminatingtheeffectofbeneficialbluelightandrosmodulatingenzymesindupuytrensdisease AT juliawille illuminatingtheeffectofbeneficialbluelightandrosmodulatingenzymesindupuytrensdisease AT joachimwindolf illuminatingtheeffectofbeneficialbluelightandrosmodulatingenzymesindupuytrensdisease AT veragrotheer illuminatingtheeffectofbeneficialbluelightandrosmodulatingenzymesindupuytrensdisease
_version_	1718375320444207104

Illuminating the effect of beneficial blue light and ROS-modulating enzymes in Dupuytren's disease.

Ejemplares similares