The autophagy-mediated mechanism via TSC1/mTOR signaling pathway in thiram-induced tibial dyschondroplasia of broilers

• Published in: The Science of the total environment Vol. 928; p. 172305
• Main Authors: Quan, Chuxian, Zhou, Shimeng, Zhang, Yan, Kulyar, Muhammad Fakhar-e-Alam, Gong, Saisai, Nawaz, Shah, Ahmed, Ahmed Ezzat, Mo, Quan, Li, Jiakui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10-06-2024
• Subjects: Autophagy; Chondrocytes; mTOR; Thiram; Tibial dyschondroplasia; Tibial dyschondroplasia; GP; TSC1; PZ; Thiram; MZ; Autophagy; S6K1; 4EBP1; TD; HZ; BV; Chondrocytes; mTOR; BMD; BMC; ULK1; ATG7; LC3; TDL; ATG5
• ISSN: 0048-9697; 1879-1026
• DOI: 10.1016/j.scitotenv.2024.172305

Thiram is a member of the dithiocarbamate family and is widely used in agriculture, especially in low-income countries. Its residues lead to various diseases, among which tibial dyschondroplasia (TD) in broiler chickens is the most common. Recent studies have also demonstrated that thiram residues may harm human health. Our previous study showed that the activity of the mTOR (mammalian target of rapamycin) signaling pathway has changed after thiram exposure. In the current study, we investigated the effect of autophagy via the mTOR signaling pathway after thiram exposure in vitro and in vivo. Our results showed that thiram inhibited the protein expression of mTOR signaling pathway-related genes such as p-4EBP1 and p-S6K1. The analysis showed a significant increase in the expression of key autophagy-related proteins, including LC3, ULK1, ATG5, and Beclin1. Further investigation proved that the effects of thiram were mediated through the downregulation of mTOR. The mTOR agonist MHY-1485 reverse the upregulation of autophagy caused by thiram in vitro. Moreover, our experiment using knockdown of TSC1 resulted in chondrocytes expressing lower levels of autophagy. In conclusion, our results demonstrate that thiram promotes autophagy via the mTOR signaling pathway in chondrogenesis, providing a potential pharmacological target for the prevention of TD.
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•Thiram inhibits mTOR signaling pathway in tibial dyschondroplasia (TD) of broilers.•Thiram-induced autophagy is mediated through downregulation of mTOR.•Activation of mTOR reverses the autophagy levels in chondrocytes.•Knockdown of TSC1 leads to lower levels of autophagy in chondrocytes.