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MiR-15p-5p Mediates the Coordination of ICAM-1 and FAK to Promote Endothelial Cell Proliferation and Migration

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Abstract

Intercellular adhesion molecule-1 (ICAM-1) in endothelial cells is critical for neutrophil adhesion and transmigration across the endothelium. Focal adhesion kinase (FAK), which controls the turnover of focal adhesion to regulate cell adhesion and migration, plays a role in the resolution of inflammation. However, the coordinated involvement of ICAM-1 and FAK during endothelial inflammation has yet to be elucidated. This study reports that, as part of an inflammatory response, ICAM-1 controls FAK expression in endothelial cells via the microRNA miR-15b-5p. Induction of lung injury by lipopolysaccharide (LPS) resulted in higher levels of FAK expression in inflammatory tissues, while in ICAM-1 knockout mice, FAK expression was reduced in the lungs. FAK expression was also reduced in endothelial cells following ICAM-1 siRNA downregulation. Furthermore, ICAM-1 inhibited miR-15b-5p expression while increasing FAK mRNA and protein expression via binding of miR-15b-5p to the 3′ untranslated region (UTR) of FAK. ICAM-1 inhibited miR-15b-5p promoter activity and hence reduced miR-15b-5p expression. FAK increased endothelial cell proliferation and migration, whereas miR-15b-5p inhibited cell proliferation and migration. These findings indicate that the inflammatory molecule ICAM-1 regulates FAK expression via miR-15b-5p levels, which in turn controls endothelial cell proliferation and migration.

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Funding

This project was supported financially by the National Natural Science Foundation of China (NSFC) (Grant Nos. 82104178 (W. Gu) and 31372418 (G. Liu)), Bengbu Medical College Scientific and Technology Self-Innovation Foundation Program, Grant No. BYKC201903 (G. Liu), and the Natural Science Research Project of Anhui Educational Committee, Grant No. KJ2021A0768 (W. Gu).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical College, 2600 Donghai StreetAnhui Province, Bengbu, 233030, China

    Wei Gu, Li Zhang, Kang Hu, Yingying Ye & Guoquan Liu

  2. Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Anhui Province, Bengbu, 233030, China

    Wei Gu, Li Zhang, Xiaoyu Shi, Kang Hu, Yingying Ye & Guoquan Liu

  3. Department of Basic Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Hubei Province, Wuhan, 430070, China

    Xinhua Zhang & Binyu Wang

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  1. Wei Gu
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Contributions

WG and GL developed the concept and designed the studies, contributed to the data analysis and statistical analysis, and wrote and edited the manuscript. WG, LZ, XH and BY analyzed the in vivo and ex vivo studies and performed statistical analysis. LZ, XH and XY contributed to the experimental studies and data acquisition. All the authors read and approved the final manuscript.

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Correspondence to Guoquan Liu.

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The study was conducted in accordance with guidelines developed by the China Council on Animal Care and Protocol. The procedures for care and use of animals were approved by the Ethics Committee of Bengbu Medical College, and all applicable institutional and governmental regulations concerning the ethical use of animals were followed.

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Gu, W., Zhang, L., Zhang, X. et al. MiR-15p-5p Mediates the Coordination of ICAM-1 and FAK to Promote Endothelial Cell Proliferation and Migration. Inflammation 45, 1402–1417 (2022). https://doi.org/10.1007/s10753-022-01630-3

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