Beclin1 regulates yak endometrial inflammation and TLR4/NF-κB signaling pathway through autophagy/non-autophagy function

Wenbin Ma; Libin Wang; Yangyang Pan; Meng Wang; Jinglei Wang; Min Feng; Junqian Wang; Hui Zhang; Rui Zhang; Zhengxing Jiao; Yan Cui; Sijiu Yu

doi:10.1016/j.intimp.2024.113940

Beclin1 regulates yak endometrial inflammation and TLR4/NF-κB signaling pathway through autophagy/non-autophagy function

Int Immunopharmacol. 2025 Jan 6:147:113940. doi: 10.1016/j.intimp.2024.113940. Online ahead of print.

Authors

Wenbin Ma¹, Libin Wang¹, Yangyang Pan¹, Meng Wang¹, Jinglei Wang², Min Feng³, Junqian Wang¹, Hui Zhang¹, Rui Zhang¹, Zhengxing Jiao¹, Yan Cui⁴, Sijiu Yu⁵

Affiliations

¹ College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China; Gansu Innovation Centre for Livestock Embryo Engineering and Technology, Lanzhou, China.
² College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an, China.
³ College of Animal Science and Technology, Ningxia University, Yinchuan, China.
⁴ College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China; Gansu Innovation Centre for Livestock Embryo Engineering and Technology, Lanzhou, China. Electronic address: cuiyan369@sina.com.
⁵ College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China; Gansu Innovation Centre for Livestock Embryo Engineering and Technology, Lanzhou, China. Electronic address: sijiuy@126.com.

PMID: 39764999
DOI: 10.1016/j.intimp.2024.113940

Abstract

Beclin1 is an autophagy related factor, and it is capable of mediating non-autophagy functions, too. Yak endometritis represents a significant obstetric ailment that impedes the normal breeding process. The current understanding of the beclin1 effect on endometrial inflammation in yak remains limited. Accordingly, this study initially examined the expression profile of beclin1 in yak endometritis in vitro and vivo. Subsequently, the beclin1 was targeted inhibit through small interfering RNA (siRNA), with the objective of elucidating the regulatory function of beclin1 in yak endometritis. The findings reveal that expression of beclin1 in inflammatory tissues of yak endometrium is markedly elevate in comparison to control group, and predominant localization in the cytoplasm of the endometrium and uterine glands. 1 µg/mL Lipopolysaccharide (LPS) was demonstrated to induce yak endometrial epithelial cells (YEECs) inflammation and increase the expression of beclin1. YEECs are disposed with 1 μg/mL LPS, resulting in a gradual increase of p62 expression from 0 h to 6 h, and significant decrease at 12 h, at 9 h to 12 h the expression of LC3 significant increase. These findings indicate that LPS impairs autophagy during the initial stages of inflammation, complete autophagy is occurred in cells during the subsequent phase. Initial stages of inflammation, inhibit beclin1 result significantly reduced expression of inflammatory factors (TNF-α and IL-1β) and TLR4/NF-κB signaling pathway (p65, IκBα phosphorylation, p65 nuclear translocation) compared to the control group. When complete autophagy occurred, inhibit beclin1 inhibit autophagy, result in a significantly higher expression of inflammatory factors (TNF-α and IL-1β) and TLR4/NF-κB signaling pathway than the control group. In conclusion, this study demonstrates for the beclin1 exerts both autophagic and non-autophagic functions during the inflammatory process in YEECs, making it become a potential target for the cure and diagnosis of various yak endometritis.

Keywords: Autophagy; Beclin1; Endometritis; NF-κB; Yak.