All-Trans Retinoic Acid Attenuates Transmissible Gastroenteritis Virus-Induced Apoptosis in IPEC-J2 Cells via Inhibiting ROS-Mediated P<sub>38</sub>MAPK Signaling Pathway
Junning Pu,
Daiwen Chen,
Gang Tian,
Jun He,
Zhiqing Huang,
Ping Zheng,
Xiangbing Mao,
Jie Yu,
Junqiu Luo,
Yuheng Luo,
Hui Yan,
Bing Yu
Affiliations
Junning Pu
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Daiwen Chen
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Gang Tian
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Jun He
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Zhiqing Huang
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Ping Zheng
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Xiangbing Mao
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Jie Yu
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Junqiu Luo
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Yuheng Luo
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Hui Yan
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Bing Yu
Key Laboratory for Animal Disease-Resistance Nutrition, Ministry of Education/Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China
Transmissible gastroenteritis virus (TGEV) can cause diarrhea, dehydration, and high mortality in piglets, which is closely related to intestinal epithelial cell apoptosis caused by TGEV infection. All-trans retinoic acid (ATRA) is the active metabolite of vitamin A, which has antioxidant and anti-apoptotic properties. However, it is unknown whether ATRA can attenuate TGEV-induced IPEC-J2 cells apoptosis. Therefore, we investigated the protective effects of ATRA on TGEV-induced apoptosis of IPEC-J2 cells and explored the potential molecular mechanism. Our results indicated that TGEV infection caused IPEC-J2 cells damage and apoptosis. However, ATRA treatment attenuated TGEV-induced IPEC-J2 cells damage by upregulating the mRNA expressions of ZO-1, Occludin, and Mucin-1. ATRA treatment also attenuated TGEV-induced apoptosis in IPEC-J2 cells by downregulating the expression of Caspase-3, which is related to the inhibition of death receptor (Fas and Caspase-8) and mitochondrial (Bax, Bcl-2, and Caspase-9) pathways. Moreover, ATRA treatment prevented TGEV-induced ROS and MDA production and the upregulation of P38MAPK phosphorylation level, which is related to the increase in the activities of antioxidant enzymes (SOD, CAT, and T-AOC) and the mRNA abundance of antioxidant-related genes (GPX1, GPX2, SOD1, CAT, GCLC, and GCLM). In addition, treatment of TGEV-infected IPEC-J2 cells with the ROS inhibitors (NAC) significantly reduced the protein levels of p-P38MAPK, Fas, Bax, and Cleaved-caspase-3 and the percentage of apoptotic cells. Our results indicated that ATRA attenuated TGEV-induced apoptosis in IPEC-J2 cells via improving the antioxidant capacity, thereby inhibiting the cell damage. the mechanism of which is associated with the inhibition of ROS-mediated P38MAPK signaling pathway.
