Abstract
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.
Highlights
Transmissible gastroenteritis virus (TGEV) is a coronavirus with a single-stranded positive-sense RNA genome [1]
We found that TGEV infection significantly increased the Lactate dehydrogenase (LDH) activity in IPEC-J2 cell culture medium, whereas All-trans retinoic acid (ATRA) treatment significantly reduced the activity of LDH in TGEVinfected IPEC-J2 cell culture medium in a dose-dependent manner
Similar results reported that ATRA treatment significantly suppressed the cytopathic effects (CPE) and apoptosis in PC12 cells following oxygen and glucose deprivation injury [39]. These results indicated that ATRA may attenuate TGEV-induced IPEC-J2 cells damage via suppressing apoptosis
Summary
Transmissible gastroenteritis virus (TGEV) is a coronavirus with a single-stranded positive-sense RNA genome [1]. TGEV replicates in enterocytes covering porcine small intestinal villi, provokes villous atrophy and cryptal cells hyperplasia, causing diarrhea, dehydration and vomiting in piglets and resulting in significant economic losses to the global pig industry [2]. Consistent with pathological changes in vivo, TGEV infection induces the cytopathic effects (CPE) of host cells in vitro [3,4], which may be related to apoptosis induced by TGEV infection. A large number of studies have reported infections with swine enteropathogenic coronaviruses such as porcine epidemic diarrhea virus (PEDV) [7], Antioxidants 2022, 11, 345. Antioxidants 2022, 11, 345 porcine delta coronavirus (PDCoV) [8], and swine acute diarrhea syndrome coronavirus (SADS-CoV) [9], resulted in host cell apoptosis.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
