PPAR-γ with its anti-fibrotic action could serve as an effective therapeutic target in T-2 toxin-induced cardiac fibrosis of rats
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články
Odkazy
PubMed
33836209
DOI
10.1016/j.fct.2021.112183
PII: S0278-6915(21)00216-7
Knihovny.cz E-zdroje
- Klíčová slova
- Cardiac fibrosis, PPAR-γ, T-2 toxin, TGF-β1, Therapeutic target,
- MeSH
- anilidy farmakologie MeSH
- buněčné linie MeSH
- fibróza chemicky indukované komplikace metabolismus patologie MeSH
- kardiomyopatie chemicky indukované komplikace metabolismus patologie MeSH
- kolagen metabolismus MeSH
- krysa rodu Rattus MeSH
- myokard metabolismus patologie MeSH
- pioglitazon farmakologie MeSH
- potkani Wistar MeSH
- PPAR gama agonisté antagonisté a inhibitory metabolismus MeSH
- signální transdukce účinky léků MeSH
- T-2 toxin toxicita MeSH
- transformující růstový faktor beta1 metabolismus MeSH
- upregulace účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 2-chloro-5-nitrobenzanilide MeSH Prohlížeč
- anilidy MeSH
- kolagen MeSH
- pioglitazon MeSH
- PPAR gama MeSH
- PPAR gamma, rat MeSH Prohlížeč
- T-2 toxin MeSH
- transformující růstový faktor beta1 MeSH
T-2 toxin, the most virulent toxin produced by the Fusarium genus, is thought to be the main cause of fatal cardiomyopathy known as Keshan disease. However, the mechanisms of T-2 toxin-induced cardiac toxicity and possible targets for its treatment remain unclear. In the present study, male Wistar rats were administered with 2 mg/kg b. w. T-2 toxin (i.g.) and sacrificed on day 7 after exposure. The hematological indices (CK, LDH) and electrocardiogram were significantly abnormal, the ultrastructure of mitochondria in the heart was changed, and the percentage of collagen area was significantly increased in the T-2 toxin-treated group. Meanwhile, T-2 toxin activated the TGF-β1/Smad2/3 signalling pathway, and also activated PPAR-γ expression in rats and H9C2 cells. Further application of PPAR-γ agonist (pioglitazone) and antagonist (GW9662) in H9C2 cells revealed that the up-regulation of PPAR-γ expression induced by T-2 toxin is a self-preservation phenomenon, and increasing exogenous PPAR-γ can alleviate the increase in TGF-β1 caused by T-2 toxin, thereby playing a role in relieving cardiac fibrosis. These findings for the first time demonstrate that T-2 toxin can regulate the expression of PPAR-γ and that PPAR-γ has the potential to serve as an effective therapeutic target in T-2 toxin-induced cardiac fibrosis of rats.