PAKISTAN VETERINARY JOURNAL

Pak Vet J, 2025, 45(4) 1572-1587

MIR-128 Targets GAREM to Regulate the ERK/MAPK Signaling Pathway and Alleviate Yak Endometritis

Hailong Dong^1,2#, Qiqi Cao^1#, Shuo Wang², Ruidong Liu², Mikhlid H. Almutairi³ and Chuang Xu^1*

¹State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, 100193 Beijing, China; ²Key Laboratory for Prevention and Control of Hydatid Disease in Xizang (Co-constructed by Ministry and Province), Ministry of Agriculture and Rural Affairs, College of Animal Science, Xizang Agricultural and Animal Husbandry University, Linzhi, 860000, China; ³Zoology Department, College of Science, King Saud University, P.O. Box: 2455, 11451, Riyadh, Saudi Arabia. ^#Hailong Dong and Qiqi Cao contributed equally to this work

*Corresponding author: xuchuang@cau.edu.cn

Abstract

Endometritis is a serious postpartum inflammatory disease that poses a significant threat to the reproductive health of cows and results in considerable economic losses. MicroRNA (miRNA) has been demonstrated to be important in the occurrence and progression of various diseases, but there is limited research on miRNA in the context of yak endometritis. Thus, this study aims to investigate whether miR-128 can influence yak endometritis by regulating the ERK/MAPK pathway via the targeting of GAREM. In-vivo studies indicated that endometritis could cause uterine damage in yaks and significantly decrease the expression of miR-128, while levels of TNF-α, IL-6, and IL-1β are dramatically increased. In vitro cell experiments demonstrated that the overexpression of miR-128 significantly reduced the expression of associated proteins and inflammatory factors within the MAPK pathway, whereas the inhibition of miR-128 resulted in increased inflammation. Furthermore, we identified GAREM as a target gene of miR-128. Notably, the suppression of GAREM expression significantly decreased the levels of related proteins in the MAPK signaling pathway and further caused a sharp decline in the expression of inflammatory factors. On the other hand, high GAREM expression correlated with intense inflammation. Further inhibition of the pathway with JNK pathway blockers (SP600125) and p38 pathway blockers (Adezmapimod) demonstrated that overexpression of miR-128 was able to lower the protein expression of p-ERK, GAREM expression, and the expression of inflammatory factors, indicating that miR-128 targets the ERK/MAPK signaling pathway in LPS-induced yak endometritis. In conclusion, this study demonstrates that miR-128 targets GAREM in the modulation of the ERK/MAPK signaling pathway, thus influencing yak endometritis.

To Cite This Article: Dong H, Cao Q, Wang S, Liu R, Almutairi MH and Xu C, 2025. miR-128 targets GAREM to regulate the ERK/MAPK signaling pathway and alleviate yak endometritis. Pak Vet J, 45(4): 1572-1587. http://dx.doi.org/10.29261/pakvetj/2025.330

Abstract

ISSN 0253-8318 (Print)ISSN 2074-7764 (Online)

ISSN 0253-8318 (Print)
ISSN 2074-7764 (Online)