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...
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Nature Portfolio
2025-03-01
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| Online Access: | https://doi.org/10.1038/s41598-025-94595-w |
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| 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 |
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| 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 |
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| 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 |
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