MicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometrium

Abstract Reproductive disorders in dairy cows represent a significant challenge to the advancement of the dairy industry. Pregnancy success is closely related to the mechanism of immune tolerance, with the PD-1/PD-L1 signaling pathway playing a role in immune regulation, which is associated with imm...

Full description

Saved in:
Bibliographic Details
Main Authors: Jinxin Zhang, Yingfang Guo, Han Zhou, Nuoer Chen, Wen Feng, Xinyu Feng, Wenjing Liu, Ganzhen Deng
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-94595-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849390363926593536
author Jinxin Zhang
Yingfang Guo
Han Zhou
Nuoer Chen
Wen Feng
Xinyu Feng
Wenjing Liu
Ganzhen Deng
author_facet Jinxin Zhang
Yingfang Guo
Han Zhou
Nuoer Chen
Wen Feng
Xinyu Feng
Wenjing Liu
Ganzhen Deng
author_sort Jinxin Zhang
collection DOAJ
description Abstract Reproductive disorders in dairy cows represent a significant challenge to the advancement of the dairy industry. Pregnancy success is closely related to the mechanism of immune tolerance, with the PD-1/PD-L1 signaling pathway playing a role in immune regulation, which is associated with immune tolerance and pregnancy maintenance. MicroRNAs can regulate pivotal molecules within the signaling pathway, physiological activities, and disease processes. p65 and PD-L1 expression was significantly increased in the early pregnant uterine epithelium. In contrast, the expression of p65 and PD-L1 was homogeneous in the endometrial epithelium of E2 and P4 co-stimulated bEECs and changed with the stimulation time and concentration. MiR-155 expression was significantly reduced in the early pregnant uterine epithelium. p65 was identified as a molecular target of miR-155 using a dual luciferase assay and mimics/inhibitor transfection, and miR-155 inhibited p65 expression by binding to the 3’-UTR of p65 mRNA. The regulation of PD-L1 expression by p65 was confirmed through the knockdown of p65 by si-p65 and the overexpression of p65 by pcDNA3.1-p65. In the context of pregnancy, miR-155 was observed to target p65, thereby regulating PD-L1 expression at the endometrial epithelium.
format Article
id doaj-art-882c42deacbf476da8d80e5ab0aa78a9
institution Kabale University
issn 2045-2322
language English
publishDate 2025-03-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj-art-882c42deacbf476da8d80e5ab0aa78a92025-08-20T03:41:41ZengNature PortfolioScientific Reports2045-23222025-03-0115111110.1038/s41598-025-94595-wMicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometriumJinxin Zhang0Yingfang Guo1Han Zhou2Nuoer Chen3Wen Feng4Xinyu Feng5Wenjing Liu6Ganzhen Deng7Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural UniversitySchool of Physical Education and International Equestrianism, Wuhan Business UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural UniversityDepartment of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural UniversityAbstract Reproductive disorders in dairy cows represent a significant challenge to the advancement of the dairy industry. Pregnancy success is closely related to the mechanism of immune tolerance, with the PD-1/PD-L1 signaling pathway playing a role in immune regulation, which is associated with immune tolerance and pregnancy maintenance. MicroRNAs can regulate pivotal molecules within the signaling pathway, physiological activities, and disease processes. p65 and PD-L1 expression was significantly increased in the early pregnant uterine epithelium. In contrast, the expression of p65 and PD-L1 was homogeneous in the endometrial epithelium of E2 and P4 co-stimulated bEECs and changed with the stimulation time and concentration. MiR-155 expression was significantly reduced in the early pregnant uterine epithelium. p65 was identified as a molecular target of miR-155 using a dual luciferase assay and mimics/inhibitor transfection, and miR-155 inhibited p65 expression by binding to the 3’-UTR of p65 mRNA. The regulation of PD-L1 expression by p65 was confirmed through the knockdown of p65 by si-p65 and the overexpression of p65 by pcDNA3.1-p65. In the context of pregnancy, miR-155 was observed to target p65, thereby regulating PD-L1 expression at the endometrial epithelium.https://doi.org/10.1038/s41598-025-94595-wCowsEarly pregnantUterine epitheliumPD-L1miR-155p65
spellingShingle Jinxin Zhang
Yingfang Guo
Han Zhou
Nuoer Chen
Wen Feng
Xinyu Feng
Wenjing Liu
Ganzhen Deng
MicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometrium
Scientific Reports
Cows
Early pregnant
Uterine epithelium
PD-L1
miR-155
p65
title MicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometrium
title_full MicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometrium
title_fullStr MicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometrium
title_full_unstemmed MicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometrium
title_short MicroRNA-155 targets p65 to regulate PD-L1 expression in the early pregnancy endometrium
title_sort microrna 155 targets p65 to regulate pd l1 expression in the early pregnancy endometrium
topic Cows
Early pregnant
Uterine epithelium
PD-L1
miR-155
p65
url https://doi.org/10.1038/s41598-025-94595-w
work_keys_str_mv AT jinxinzhang microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium
AT yingfangguo microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium
AT hanzhou microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium
AT nuoerchen microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium
AT wenfeng microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium
AT xinyufeng microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium
AT wenjingliu microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium
AT ganzhendeng microrna155targetsp65toregulatepdl1expressionintheearlypregnancyendometrium