Baicalin modulates endoplasmic reticulum-Golgi homeostasis via targeting ATF6-GBF1 axis to alleviate copper-induced nephrotoxicity in duck.
- 1Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Economic and Technological Development District, No. 1101 Zhimin Avenue, Nanchang, Jiangxi, 330045, PR China.
- 2Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Economic and Technological Development District, No. 1101 Zhimin Avenue, Nanchang, Jiangxi, 330045, PR China. Electronic address: [email protected].
Abstract
Copper (Cu) exposure caused by environmental contamination or dietary imbalance poses a potential threat to poultry health by inducing renal dysfunction and disrupting cellular homeostasis. Baicalin (BA), a natural flavonoid with antioxidant and anti-inflammatory properties, has shown renoprotective potential. However, whether and how BA alleviates Cu-induced nephrotoxicity remains unclear. Disruption of endoplasmic reticulum (ER)-Golgi trafficking impairs cellular homeostasis and may contribute to renal injury, but its role in Cu-induced kidney damage has not been fully defined. In this study, using duck in vivo and in vitro Cu exposure models, we found that Cu downregulated the Golgi structural protein GBF1 and disrupted ER-Golgi trafficking, leading to Golgi fragmentation, ER swelling, and ER stress activation via ATF6. Functional assays revealed that GBF1 knockdown further decreased the expression of Golgi structural and trafficking-related proteins and exacerbated ER stress, whereas ATF6 silencing partially reversed these molecular alterations. Moreover, our results provide evidence that BA can stably bind to ATF6, inhibit its activation and proteolytic cleavage, restore the expression of Golgi and trafficking-related proteins, and reduce ER stress, thereby maintaining organelle homeostasis. In summary, our results identify the GBF1-ATF6 axis as a key pathway in Cu-induced ER-Golgi dysregulation and nephrotoxicity, and provide mechanistic insight into the protective role of BA in restoring subcellular homeostasis.
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BibTeX
@article{shang2026baicalin,
title = {{Baicalin modulates endoplasmic reticulum-Golgi homeostasis via targeting ATF6-GBF1 axis to alleviate copper-induced nephrotoxicity in duck.}},
author = {Hongyu Shang and Wei Tang and Xueyan Dai and Xiaona Gao and Guoliang Hu and Huabin Cao and Chenghong Xing and Fan Yang},
journal = {Poultry science},
year = {2026},
month = oct,
doi = {10.1016/j.psj.2026.107914},
url = {https://europepmc.org/article/MED/42863176},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Baicalin modulates endoplasmic reticulum-Golgi homeostasis via targeting ATF6-GBF1 axis to alleviate copper-induced nephrotoxicity in duck.
AU - Hongyu Shang
AU - Wei Tang
AU - Xueyan Dai
AU - Xiaona Gao
AU - Guoliang Hu
AU - Huabin Cao
AU - Chenghong Xing
AU - Fan Yang
PY - 2026
DA - 2026/10/08
JO - Poultry science
DO - 10.1016/j.psj.2026.107914
UR - https://europepmc.org/article/MED/42863176
AB - Copper (Cu) exposure caused by environmental contamination or dietary imbalance poses a potential threat to poultry health by inducing renal dysfunction and disrupting cellular homeostasis. Baicalin (BA), a natural flavonoid with antioxidant and anti-inflammatory properties, has shown renoprotective potential. However, whether and how BA alleviates Cu-induced nephrotoxicity remains unclear. Disruption of endoplasmic reticulum (ER)-Golgi trafficking impairs cellular homeostasis and may contribute to renal injury, but its role in Cu-induced kidney damage has not been fully defined. In this study, using duck in vivo and in vitro Cu exposure models, we found that Cu downregulated the Golgi structural protein GBF1 and disrupted ER-Golgi trafficking, leading to Golgi fragmentation, ER swelling, and ER stress activation via ATF6. Functional assays revealed that GBF1 knockdown further decreased the expression of Golgi structural and trafficking-related proteins and exacerbated ER stress, whereas ATF6 silencing partially reversed these molecular alterations. Moreover, our results provide evidence that BA can stably bind to ATF6, inhibit its activation and proteolytic cleavage, restore the expression of Golgi and trafficking-related proteins, and reduce ER stress, thereby maintaining organelle homeostasis. In summary, our results identify the GBF1-ATF6 axis as a key pathway in Cu-induced ER-Golgi dysregulation and nephrotoxicity, and provide mechanistic insight into the protective role of BA in restoring subcellular homeostasis.
SN - 0032-5791
SN - 1525-3171
ER -