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The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?

One major complication after fistulating glaucoma surgeries are fibroblast-mediated scarring processes and their specific prevention is key in the development of novel pharmaceutical concepts. Within this study a possible antifibrotic potential of kitasamycin (KM) in a transforming growth factor (TG...

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Autores principales: Sterenczak, Katharina A., Fuellen, Georg, Jünemann, Anselm, Guthoff, Rudolf F., Stachs, Oliver, Stahnke, Thomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960401/
https://www.ncbi.nlm.nih.gov/pubmed/36839651
http://dx.doi.org/10.3390/pharmaceutics15020329
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author Sterenczak, Katharina A.
Fuellen, Georg
Jünemann, Anselm
Guthoff, Rudolf F.
Stachs, Oliver
Stahnke, Thomas
author_facet Sterenczak, Katharina A.
Fuellen, Georg
Jünemann, Anselm
Guthoff, Rudolf F.
Stachs, Oliver
Stahnke, Thomas
author_sort Sterenczak, Katharina A.
collection PubMed
description One major complication after fistulating glaucoma surgeries are fibroblast-mediated scarring processes and their specific prevention is key in the development of novel pharmaceutical concepts. Within this study a possible antifibrotic potential of kitasamycin (KM) in a transforming growth factor (TGF)-β1-mediated fibroblast model was evaluated in vitro. Primary ocular fibroblasts were isolated, cultivated and a dose–response test including determination of the half maximal effective concentration (EC50) for KM was conducted. Transformation of fibroblasts into myofibroblasts was induced by TGF-β1and immunofluorescence (IF), and Western blot (WB) analyses were performed with fibroblasts and myofibroblasts. IF analyses were carried out using antibodies against α-smooth muscle actin (α-SMA) and fibronectin, and protein detection of intracellular and extracellular proteins was performed by WB. Using the dose–response test, the viability, cytotoxicity and EC50 of KM after 24 and 48 h were determined. Fibroblasts exposed to various KM concentrations showed no increase in α-SMA and extracellular matrix expression. In TGF-ß1-stimulated myofibroblasts, KM inhibited the expression of α-SMA and fibronectin in a concentration-dependent manner. These findings demonstrate that KM could impair the transformation of fibroblasts into myofibroblasts and the expression of proteins involved in fibrotic processes, representing a potential agent for specific fibrosis prevention in future therapeutic concepts.
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spelling pubmed-99604012023-02-26 The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery? Sterenczak, Katharina A. Fuellen, Georg Jünemann, Anselm Guthoff, Rudolf F. Stachs, Oliver Stahnke, Thomas Pharmaceutics Article One major complication after fistulating glaucoma surgeries are fibroblast-mediated scarring processes and their specific prevention is key in the development of novel pharmaceutical concepts. Within this study a possible antifibrotic potential of kitasamycin (KM) in a transforming growth factor (TGF)-β1-mediated fibroblast model was evaluated in vitro. Primary ocular fibroblasts were isolated, cultivated and a dose–response test including determination of the half maximal effective concentration (EC50) for KM was conducted. Transformation of fibroblasts into myofibroblasts was induced by TGF-β1and immunofluorescence (IF), and Western blot (WB) analyses were performed with fibroblasts and myofibroblasts. IF analyses were carried out using antibodies against α-smooth muscle actin (α-SMA) and fibronectin, and protein detection of intracellular and extracellular proteins was performed by WB. Using the dose–response test, the viability, cytotoxicity and EC50 of KM after 24 and 48 h were determined. Fibroblasts exposed to various KM concentrations showed no increase in α-SMA and extracellular matrix expression. In TGF-ß1-stimulated myofibroblasts, KM inhibited the expression of α-SMA and fibronectin in a concentration-dependent manner. These findings demonstrate that KM could impair the transformation of fibroblasts into myofibroblasts and the expression of proteins involved in fibrotic processes, representing a potential agent for specific fibrosis prevention in future therapeutic concepts. MDPI 2023-01-18 /pmc/articles/PMC9960401/ /pubmed/36839651 http://dx.doi.org/10.3390/pharmaceutics15020329 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sterenczak, Katharina A.
Fuellen, Georg
Jünemann, Anselm
Guthoff, Rudolf F.
Stachs, Oliver
Stahnke, Thomas
The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?
title The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?
title_full The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?
title_fullStr The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?
title_full_unstemmed The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?
title_short The Antibiotic Kitasamycin—A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?
title_sort antibiotic kitasamycin—a potential agent for specific fibrosis preventing therapy after fistulating glaucoma surgery?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960401/
https://www.ncbi.nlm.nih.gov/pubmed/36839651
http://dx.doi.org/10.3390/pharmaceutics15020329
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