The macrocyclic lactone oxacyclododecindione reduces fibrosis progression

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Sabrina Saurin
  • Myriam Meineck
  • Markus Rohr
  • Wilfried Roth
  • Till Opatz
  • Gerhard Erkel
  • Andrea Pautz
  • Julia Weinmann-Menke
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001020633400001&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.3389/fphar.2023.1200164
eISSN
1663-9812
Externe Identifier
  • Clarivate Analytics Document Solution ID: L0ZV8
  • PubMed Identifier: 37383717
Zeitschrift
FRONTIERS IN PHARMACOLOGY
Schlüsselwörter
  • renal fibrosis
  • ischemia-reperfusion
  • epithelial-mesenchymal transition
  • macrolactone
  • chronic kidney disease
Artikelnummer
ARTN 1200164
Datum der Veröffentlichung
2023
Status
Published
Titel
The macrocyclic lactone oxacyclododecindione reduces fibrosis progression
Sub types
  • Article
Ausgabe der Zeitschrift
14

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:p><jats:bold>Background:</jats:bold> Renal fibrosis is one of the most important triggers of chronic kidney disease (CKD), and only a very limited number of therapeutic options are available to stop fibrosis progression. As fibrosis is characterized by inflammation, myofibroblast activation, and extracellular matrix (ECM) deposition, a drug that can address all these processes might be an interesting therapeutic option.</jats:p><jats:p><jats:bold>Methods:</jats:bold> We tested <jats:italic>in vivo</jats:italic> in an ischemia–reperfusion (I/R) model in C57BL/6 mice and in kidney tubular epithelial cells (TEC) (HK2 cell line and primary cells) whether the natural product oxacyclododecindione (Oxa) reduces fibrosis progression in kidney disease. This was evaluated by Western blot, mRNA expression, and mass spectrometry secretome analyses, as well as by immunohistochemistry.</jats:p><jats:p><jats:bold>Results:</jats:bold> Indeed, Oxa blocked the expression of epithelial–mesenchymal transition marker proteins and reduced renal damage, immune cell infiltration, and collagen expression and deposition, both <jats:italic>in vivo</jats:italic> and <jats:italic>in vitro</jats:italic>. Remarkably, the beneficial effects of Oxa were also detected when the natural product was administered at a time point of established fibrotic changes, a situation close to the clinical situation. Initial <jats:italic>in vitro</jats:italic> experiments demonstrated that a synthetic Oxa derivative possesses similar features.</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> Although open questions such as possible side effects need to be investigated, our results indicate that the combination of anti-inflammatory and anti-fibrotic effects of Oxa make the substance a promising candidate for a new therapeutic approach in fibrosis treatment, and thus in the prevention of kidney disease progression.</jats:p>
Autoren
  • Sabrina Saurin
  • Myriam Meineck
  • Markus Rohr
  • Wilfried Roth
  • Till Opatz
  • Gerhard Erkel
  • Andrea Pautz
  • Julia Weinmann-Menke
DOI
10.3389/fphar.2023.1200164
eISSN
1663-9812
Zeitschrift
Frontiers in Pharmacology
Online publication date
2023
Status
Published online
Herausgeber
Frontiers Media SA
Herausgeber URL
http://dx.doi.org/10.3389/fphar.2023.1200164
Datum der Datenerfassung
2023
Titel
The macrocyclic lactone oxacyclododecindione reduces fibrosis progression
Ausgabe der Zeitschrift
14

Datenquelle: Crossref

Abstract
<b>Background:</b> Renal fibrosis is one of the most important triggers of chronic kidney disease (CKD), and only a very limited number of therapeutic options are available to stop fibrosis progression. As fibrosis is characterized by inflammation, myofibroblast activation, and extracellular matrix (ECM) deposition, a drug that can address all these processes might be an interesting therapeutic option. <b>Methods:</b> We tested <i>in vivo</i> in an ischemia-reperfusion (I/R) model in C57BL/6 mice and in kidney tubular epithelial cells (TEC) (HK2 cell line and primary cells) whether the natural product oxacyclododecindione (Oxa) reduces fibrosis progression in kidney disease. This was evaluated by Western blot, mRNA expression, and mass spectrometry secretome analyses, as well as by immunohistochemistry. <b>Results:</b> Indeed, Oxa blocked the expression of epithelial-mesenchymal transition marker proteins and reduced renal damage, immune cell infiltration, and collagen expression and deposition, both <i>in vivo</i> and <i>in vitro</i>. Remarkably, the beneficial effects of Oxa were also detected when the natural product was administered at a time point of established fibrotic changes, a situation close to the clinical situation. Initial <i>in vitro</i> experiments demonstrated that a synthetic Oxa derivative possesses similar features. <b>Conclusion:</b> Although open questions such as possible side effects need to be investigated, our results indicate that the combination of anti-inflammatory and anti-fibrotic effects of Oxa make the substance a promising candidate for a new therapeutic approach in fibrosis treatment, and thus in the prevention of kidney disease progression.
Addresses
  • Department of Nephrology, Center of Immunotherapy, Medical Center of the Johannes-Gutenberg University Mainz, Mainz, Germany.
Autoren
  • Sabrina Saurin
  • Myriam Meineck
  • Markus Rohr
  • Wilfried Roth
  • Till Opatz
  • Gerhard Erkel
  • Andrea Pautz
  • Julia Weinmann-Menke
DOI
10.3389/fphar.2023.1200164
eISSN
1663-9812
Externe Identifier
  • PubMed Identifier: 37383717
  • PubMed Central ID: PMC10294233
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: WE 5779/4-1 ER 176/12-1
Open access
true
ISSN
1663-9812
Zeitschrift
Frontiers in pharmacology
Sprache
eng
Medium
Electronic-eCollection
Online publication date
2023
Open access status
Open Access
Paginierung
1200164
Datum der Veröffentlichung
2023
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2023
Titel
The macrocyclic lactone oxacyclododecindione reduces fibrosis progression.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
14

Files

https://www.frontiersin.org/articles/10.3389/fphar.2023.1200164/pdf https://europepmc.org/articles/PMC10294233?pdf=render

Datenquelle: Europe PubMed Central

Abstract
Background: Renal fibrosis is one of the most important triggers of chronic kidney disease (CKD), and only a very limited number of therapeutic options are available to stop fibrosis progression. As fibrosis is characterized by inflammation, myofibroblast activation, and extracellular matrix (ECM) deposition, a drug that can address all these processes might be an interesting therapeutic option. Methods: We tested in vivo in an ischemia-reperfusion (I/R) model in C57BL/6 mice and in kidney tubular epithelial cells (TEC) (HK2 cell line and primary cells) whether the natural product oxacyclododecindione (Oxa) reduces fibrosis progression in kidney disease. This was evaluated by Western blot, mRNA expression, and mass spectrometry secretome analyses, as well as by immunohistochemistry. Results: Indeed, Oxa blocked the expression of epithelial-mesenchymal transition marker proteins and reduced renal damage, immune cell infiltration, and collagen expression and deposition, both in vivo and in vitro. Remarkably, the beneficial effects of Oxa were also detected when the natural product was administered at a time point of established fibrotic changes, a situation close to the clinical situation. Initial in vitro experiments demonstrated that a synthetic Oxa derivative possesses similar features. Conclusion: Although open questions such as possible side effects need to be investigated, our results indicate that the combination of anti-inflammatory and anti-fibrotic effects of Oxa make the substance a promising candidate for a new therapeutic approach in fibrosis treatment, and thus in the prevention of kidney disease progression.
Date of acceptance
2023
Autoren
  • Sabrina Saurin
  • Myriam Meineck
  • Markus Rohr
  • Wilfried Roth
  • Till Opatz
  • Gerhard Erkel
  • Andrea Pautz
  • Julia Weinmann-Menke
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/37383717
DOI
10.3389/fphar.2023.1200164
Externe Identifier
  • PubMed Central ID: PMC10294233
ISSN
1663-9812
Zeitschrift
Front Pharmacol
Schlüsselwörter
  • chronic kidney disease
  • epithelial–mesenchymal transition
  • ischemia–reperfusion
  • macrolactone
  • renal fibrosis
Sprache
eng
Country
Switzerland
Paginierung
1200164
PII
1200164
Datum der Veröffentlichung
2023
Status
Published online
Titel
The macrocyclic lactone oxacyclododecindione reduces fibrosis progression.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
14

Datenquelle: PubMed

Author's licence
CC-BY
Autoren
  • Sabrina Saurin
  • Myriam Meineck
  • Markus Rohr
  • Wilfried Roth
  • Till Opatz
  • Gerhard Erkel
  • Andrea Pautz
  • Julia Weinmann-Menke
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.3389/fphar.2023.1200164
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft (DFG)|491381577|Open-Access-Publikationskosten 2022–2024 Universität Mainz - Universitätsmedizin
File(s) embargoed
false
Open access
true
ISSN
1663-9812
Zeitschrift
Frontiers in pharmacology
Schlüsselwörter
  • 610 Medizin
  • 610 Medical sciences
Sprache
eng
Open access status
Open Access
Paginierung
1200164
Datum der Veröffentlichung
2023
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/10016
Herausgeber
Frontiers Media
Datum der Datenerfassung
2024
Datum, an dem der Datensatz öffentlich gemacht wurde
2024
Zugang
Public
Titel
The macrocyclic lactone oxacyclododecindione reduces fibrosis progression
Ausgabe der Zeitschrift
14

Files

the_macrocyclic_lactone_oxacy-20240131170453128.pdf

Datenquelle: OPENSCIENCE.UB

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