Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1784895505512267776 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9960401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT sterenczakkatharinaa theantibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT fuellengeorg theantibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT junemannanselm theantibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT guthoffrudolff theantibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT stachsoliver theantibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT stahnkethomas theantibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT sterenczakkatharinaa antibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT fuellengeorg antibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT junemannanselm antibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT guthoffrudolff antibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT stachsoliver antibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery AT stahnkethomas antibiotickitasamycinapotentialagentforspecificfibrosispreventingtherapyafterfistulatingglaucomasurgery |