Comparative transcriptomic analysis reveals the protective mechanism of ferulic acid against lipopolysaccharide-induced ferroptosis in IPEC-J2 cells
4 affiliations
- 1College of Animal Science, Inner Mongolia Agricultural University, Hohhot, China
- 2Laboratory of Smart Animal Husbandry at Universities of Inner Mongolia Autonomous Region, Hohhot, China
- 3Dairy-Breeding and Production Research Subcenter of National Technology Innovation Center for Dairy, Hohhot, China
- 4State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China
Abstract
Lipopolysaccharide (LPS) is a key virulence factor that induces intestinal oxidative damage in livestock and poultry, and cellular ferroptosis is one of the triggers of oxidative stress. Ferulic acid (FA) is a natural phenolic acid with antioxidant, anti-inflammatory and anti-ferroptosis properties. This study aimed to investigate the protective effects of FA against LPS-induced ferroptosis in the porcine small intestinal epithelial cell line (IPEC-J2) and to elucidate the underlying mechanisms. The experiment included four treatment groups: control group (CON), 50 μg/mL FA group (FA), 10 μg/mL LPS group (LPS), and 50 μg/mL FA combined with 10 μg/mL LPS group (FA and LPS), with all treatments lasting 24 h. The results showed that FA inhibited ferroptosis in IPEC-J2 cells. LPS successfully induced ferroptosis, as evidenced by decreased cell viability, increased levels of ROS, MDA, and Fe2+, downregulation of GPX4 and SLC7A11, and upregulation of TFRC and ACSL4. FA effectively alleviated LPS-induced ferroptosis in IPEC-J2 cells, with an efficacy comparable to that of the ferroptosis inhibitor Fer-1. Transcriptomic analysis revealed that FA significantly reversed the gene expression changes induced by LPS, with differentially expressed genes enriched in pathways related to ferroptosis, TNF signaling, NF-κB signaling, arachidonic acid metabolism, and PI3K-Akt signaling. Protein–protein interaction (PPI) network analysis indicated that genes such as HMGCS1, CXCL8, and IL-18 may serve as key nodes mediating the protective effects of FA. In conclusion, FA alleviates LPS-induced ferroptosis in IPEC-J2 cells by regulating glutathione metabolism, maintaining iron homeostasis, and inhibiting lipid peroxidation. This effect is closely associated with the coordinated regulation of inflammatory responses, lipid metabolism, and ferroptosis-related signaling pathways.
Related
- Mechanisms of ferroptosis in Echinococcus granulosus cyst fluid-induced hepatic injury and the protective role of Nrf2 activation.
- ZFP36-ferroptosis axis as a key renal protective pathway in diabetic kidney disease
- Hippo pathway in cancer ferroptosis: from mechanism insights to targeted therapies
- Transcriptomic Profiling Identifies Hub Transcription Factors Associated with the Protective Effects of Licochalcone A Against HFD-Induced MASLD
- Exploring the protective mechanism of Huangqishengmaiyin against anthracycline-induced cardiotoxicity in breast cancer with concomitant gut microbiota modulation
BibTeX
@article{chen2026comparative,
title = {{Comparative transcriptomic analysis reveals the protective mechanism of ferulic acid against lipopolysaccharide-induced ferroptosis in IPEC-J2 cells}},
author = {Jiayu Chen and Hongchao Li and Yaxuan Niu and Tao Guo and Xiangyu Wang and Yue Zhang and Wenwen Wang and Yuanqing Xu and Yuan Wang and Mingxing Chu},
journal = {Frontiers in Veterinary Science},
year = {2026},
month = oct,
doi = {10.3389/fvets.2026.1950560},
url = {https://doi.org/10.3389/fvets.2026.1950560},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative transcriptomic analysis reveals the protective mechanism of ferulic acid against lipopolysaccharide-induced ferroptosis in IPEC-J2 cells
AU - Jiayu Chen
AU - Hongchao Li
AU - Yaxuan Niu
AU - Tao Guo
AU - Xiangyu Wang
AU - Yue Zhang
AU - Wenwen Wang
AU - Yuanqing Xu
AU - Yuan Wang
AU - Mingxing Chu
PY - 2026
DA - 2026/10/12
JO - Frontiers in Veterinary Science
DO - 10.3389/fvets.2026.1950560
UR - https://doi.org/10.3389/fvets.2026.1950560
AB - Lipopolysaccharide (LPS) is a key virulence factor that induces intestinal oxidative damage in livestock and poultry, and cellular ferroptosis is one of the triggers of oxidative stress. Ferulic acid (FA) is a natural phenolic acid with antioxidant, anti-inflammatory and anti-ferroptosis properties. This study aimed to investigate the protective effects of FA against LPS-induced ferroptosis in the porcine small intestinal epithelial cell line (IPEC-J2) and to elucidate the underlying mechanisms. The experiment included four treatment groups: control group (CON), 50 μg/mL FA group (FA), 10 μg/mL LPS group (LPS), and 50 μg/mL FA combined with 10 μg/mL LPS group (FA and LPS), with all treatments lasting 24 h. The results showed that FA inhibited ferroptosis in IPEC-J2 cells. LPS successfully induced ferroptosis, as evidenced by decreased cell viability, increased levels of ROS, MDA, and Fe2+, downregulation of GPX4 and SLC7A11, and upregulation of TFRC and ACSL4. FA effectively alleviated LPS-induced ferroptosis in IPEC-J2 cells, with an efficacy comparable to that of the ferroptosis inhibitor Fer-1. Transcriptomic analysis revealed that FA significantly reversed the gene expression changes induced by LPS, with differentially expressed genes enriched in pathways related to ferroptosis, TNF signaling, NF-κB signaling, arachidonic acid metabolism, and PI3K-Akt signaling. Protein–protein interaction (PPI) network analysis indicated that genes such as HMGCS1, CXCL8, and IL-18 may serve as key nodes mediating the protective effects of FA. In conclusion, FA alleviates LPS-induced ferroptosis in IPEC-J2 cells by regulating glutathione metabolism, maintaining iron homeostasis, and inhibiting lipid peroxidation. This effect is closely associated with the coordinated regulation of inflammatory responses, lipid metabolism, and ferroptosis-related signaling pathways.
SN - 2297-1769
ER -