TGFβ2 and TGFβ3 mediate appropriate context-dependent phenotype of rat valvular interstitial cells.
cell biology
molecular biology
molecular physiology
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
19 Mar 2021
19 Mar 2021
Historique:
received:
03
03
2020
revised:
21
11
2020
accepted:
27
01
2021
entrez:
5
3
2021
pubmed:
6
3
2021
medline:
6
3
2021
Statut:
epublish
Résumé
This study focused on characterizing the potential mechanism of valvular toxicity caused by TGFβ receptor inhibitors (TGFβRis) using rat valvular interstitial cells (VICs) to evaluate early biological responses to TGFβR inhibition. Three TGFβRis that achieved similar exposures in the rat were assessed. Two dual TGFβRI/-RII inhibitors caused valvulopathy, whereas a selective TGFβRI inhibitor did not, leading to a hypothesis that TGFβ receptor selectivity may influence the potency of valvular toxicity. The dual valvular toxic inhibitors had the most profound effect on altering VIC phenotype including altered morphology, migration, and extracellular matrix production. Reduction of TGFβ expression demonstrated that combined TGFβ2/β3 inhibition by small interfering RNA or neutralizing antibodies caused similar alterations as TGFβRis. Inhibition of
Identifiants
pubmed: 33665554
doi: 10.1016/j.isci.2021.102133
pii: S2589-0042(21)00101-2
pmc: PMC7900227
doi:
Types de publication
Journal Article
Langues
eng
Pagination
102133Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
All authors are employees of BMS and may own shares of company stocks, but there are no conflicts of interest in regard to the disclosure of data associated with this study.
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