4-Phenylbutyric Acid Attenuates Soybean Glycinin/β-Conglycinin-Induced IPEC-J2 Cells Apoptosis by Regulating the Mitochondria-Associated Endoplasmic Reticulum Membrane and NLRP-3.

Abstract

Glycinin (11S) and β-conglycinin (7S) from soybean (glycine max) cause diarrhea and intestinal barrier damage in young animals. Understanding the mechanisms underlying the damage caused by 7S and 11S, it is vital to develop strategies to eliminate allergenicity. Consequently, we investigated 7S/11S-mediated apoptosis in porcine intestinal epithelial (IPEC-J2) cells. IPEC-J2 cells suffered endoplasmic reticulum stress (ERS) in response to 7S and 11S, activating protein kinase RNA-like ER kinase, activating transcription factor 6, C/EBP homologous protein, and inositol-requiring enzyme 1 alpha. 4-Phenylbutyric acid (4-PBA) treatment alleviated ERS; reduced the NLR family pyrin domain containing 3, interleukin-1β, and interleukin-18 levels; inhibited apoptosis; increased mitofusin 2 expression; and mitigated Ca2+ overload and mitochondria-associated ER membrane (MAM) dysfunction, thereby ameliorating IPEC-J2 injury. We demonstrated the pivotal role of ERS in MAM dysfunction and 7S- and 11S-mediated apoptosis, providing insights into 7S- and 11S-mediated intestinal barrier injury prevention and treatment.