Stanniocalcin 2 regulates autophagy and ferroptosis in mammary epithelial cells of dairy cows through the mTORC1 pathway

Stanniocalcin 2 (STC2), a glycoprotein hormone, is extensively expressed in various organs and tissues, particularly in the mammary gland. STC2 plays a crucial role in enabling cells to adapt to stress conditions and avert apoptosis. The efficiency of milk production is closely linked to both the qu...

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Bibliographic Details
Published in:The Journal of nutrition 2024-04
Main Authors: Li, RongNuo, Geng, HuiJun, Tan, Xiao, Wang, JiangXin, Deng, Lu
Format: Article
Language:English
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Summary:Stanniocalcin 2 (STC2), a glycoprotein hormone, is extensively expressed in various organs and tissues, particularly in the mammary gland. STC2 plays a crucial role in enabling cells to adapt to stress conditions and avert apoptosis. The efficiency of milk production is closely linked to both the quantity and quality of mammary cells. Yet there remains a dearth of research on the impact of STC2 on mammary cells activity in dairy cows. The objective of this study was to investigate the effects of STC2 on the viability of mammary epithelial cells in dairy cows and to elucidate the underlying mechanisms. Firstly, the GEPIA database was employed to perform survival analysis on STC2 expression in relation to prognosis using TCGA and GETx data. Subsequently, the basic physical and chemical properties, gene expression, and potential signaling pathways involved in the growth of dairy cow mammary epithelial cells were determined using STC2 knockdown. STC2 knockdown significantly suppressed autophagy in mammary epithelial cells of dairy cows. Moreover, STC2 knockdown upregulated GPX4 protein expression, elicited an elevation in Lipid ROS levels, and inhibited the mTORC1 signaling pathway, consequently repressing downstream genes involved in lipid synthesis regulated by mTORC1 and ultimately inducing ferroptosis. The findings of our study suggest that STC2 suppresses autophagy and ferroptosis through the activation of mTORC1. Mechanically, STC2 exerts an inhibitory effect on ferroptosis by activating antioxidative stress-related proteins, such as GPX4, to suppress Lipid ROS production and stimulating the mTORC1 signaling pathway to enhance the expression of genes associated with lipid synthesis.
ISSN:1541-6100
DOI:10.1016/j.tjnut.2024.04.022