PPAR-γ with its anti-fibrotic action could serve as an effective therapeutic target in T-2 toxin-induced cardiac fibrosis of rats
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
PubMed
33836209
DOI
10.1016/j.fct.2021.112183
PII: S0278-6915(21)00216-7
Knihovny.cz E-resources
- Keywords
- Cardiac fibrosis, PPAR-γ, T-2 toxin, TGF-β1, Therapeutic target,
- MeSH
- Anilides pharmacology MeSH
- Cell Line MeSH
- Fibrosis chemically induced complications metabolism pathology MeSH
- Cardiomyopathies chemically induced complications metabolism pathology MeSH
- Collagen metabolism MeSH
- Rats MeSH
- Myocardium metabolism pathology MeSH
- Pioglitazone pharmacology MeSH
- Rats, Wistar MeSH
- PPAR gamma agonists antagonists & inhibitors metabolism MeSH
- Signal Transduction drug effects MeSH
- T-2 Toxin toxicity MeSH
- Transforming Growth Factor beta1 metabolism MeSH
- Up-Regulation drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 2-chloro-5-nitrobenzanilide MeSH Browser
- Anilides MeSH
- Collagen MeSH
- Pioglitazone MeSH
- PPAR gamma MeSH
- PPAR gamma, rat MeSH Browser
- T-2 Toxin MeSH
- Transforming Growth Factor 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.
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