Propofol Suppresses LPS-induced BBB Damage by Regulating miR-130a-5p/ZO-1 Axis.

Publisher: Springer Country of Publication: Switzerland NLM ID: 9423533 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-0305 (Electronic) Linking ISSN: 10736085 NLM ISO Abbreviation: Mol Biotechnol Subsets: MEDLINE

Publication: [Cham] : Springer
Original Publication: Totowa, NJ : Humana Press, c1994-

Blood-Brain Barrier*/metabolism ; Blood-Brain Barrier*/drug effects ; Endothelial Cells*/metabolism ; Endothelial Cells*/drug effects ; MicroRNAs*/genetics ; MicroRNAs*/metabolism ; Propofol*/pharmacology ; Zonula Occludens-1 Protein*/metabolism ; Zonula Occludens-1 Protein*/genetics; Animals ; Humans ; Male ; Mice ; Cell Line ; Interleukin-1beta/metabolism ; Interleukin-1beta/genetics ; Lipopolysaccharides/adverse effects ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha/metabolism ; Tumor Necrosis Factor-alpha/genetics

The blood-brain barrier (BBB) is a highly selective semi-permeable barrier that separates circulating blood from the extracellular fluid of the brain and central nervous system, which is crucial for maintaining brain homeostasis. This study aimed to explore the role of propofol in BBB damage and further evaluate the underlying molecular mechanism. Lipopolysaccharide (LPS) was administered to mice to create an in vivo BBB damage mice model. Additionally, hCMEC/D3 cells as brain microvascular endothelial cells (BMECs) were treated with LPS to establish the in vitro BBB damage cell model. Subsequently, propofol was used for the BBB damage model. Evans blue staining and fluorescein sodium were utilized in the in vivo experiments to demonstrate BBB leakage and BBB permeability. Cell counting kit-8 (CCK-8) assay was used to assess cell viability and the trans-endothelial electrical resistance (TEER) value was measured using an epithelial voltmeter. Furthermore, enzyme-linked immunosorbent assay was performed to measure the levels of the inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). The levels of miR-130a-5p and zonula occludens-1 (ZO-1) in brain tissues and cells were detected using reverse transcription-quantitative polymerase chain reaction, western blot, or immunofluorescence staining. Furthermore, a dual-luciferase reporter assay was used to demonstrate the association between miR-130a-5p and ZO-1. Propofol treatment suppressed BBB leakage, the amount of fluorescein sodium, and the levels of IL-1β and TNF-α in the LPS-induced BBB damage mice model. Meanwhile, propofol treatment increased the TEER value in the LPS-induced hCMEC/D3 cells. Additionally, propofol treatment significantly down-regulated miR-130a-5p and up-regulated ZO-1. More importantly, miR-130a-5p directly targeted ZO-1 and negatively regulated ZO-1 expression in hCMEC/D3 cells. Furthermore, miR-130a-5p mimic partially reversed the effect of propofol on the TEER value and the levels of inflammatory cytokines such as IL-1β and TNF-α in the LPS-induced hCMEC/D3 cells. Propofol suppressed LPS-induced BBB damage by regulating miR-130a-5p/ZO-1 axis. These findings suggested a potentially effective treatment approach for BBB damage.
(© 2023. The Author(s).)

Profaci, C. P., Munji, R. N., Pulido, R. S., & Daneman, R. (2020). title. The Journal of experimental medicine 217.
Kadry, H., Noorani, B., & Cucullo, L. (2020). Title. Fluids and barriers of the CNS, 17, 69. (PMID: 10.1186/s12987-020-00230-3332081417672931)
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2018). title. Nature reviews. Neurology 14, 133–150.
Abdullahi, W., Tripathi, D., & Ronaldson, P. T. (2018). title. American journal of physiology. Cell physiology 315, C343-c356.
Xu, L., Nirwane, A., & Yao, Y. (2019). Title. Stroke and vascular neurology, 4, 78–82. (PMID: 10.1136/svn-2018-00019831338215)
Zhang, Y., Li, X., Qiao, S., Yang, D., Li, Z., Xu, J., Li, W., Su, L., & Liu, W. (2021). Title. Journal of neurochemistry, 156, 352–366. (PMID: 10.1111/jnc.1510232531803)
Berndt, P., Winkler, L., Cording, J., Breitkreuz-Korff, O., Rex, A., Dithmer, S., Rausch, V., Blasig, R., Richter, M., Sporbert, A., Wolburg, H., Blasig, I. E., & Haseloff, R. F. (2019). title. Cellular and molecular life sciences: CMLS 76, 1987–2002.
Winkler, L., Blasig, R., Breitkreuz-Korff, O., Berndt, P., Dithmer, S., Helms, H. C., Puchkov, D., Devraj, K., Kaya, M., Qin, Z., Liebner, S., Wolburg, H., Andjelkovic, A. V., Rex, A., Blasig, I. E., & Haseloff, R. F. (2021). title. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 41, 132–145.
Pan, J., Qu, M., Li, Y., Wang, L., Zhang, L., Wang, Y., Tang, Y., Tian, H. L., Zhang, Z., & Yang, G. Y. (2020). title. Stroke 51, 619–627.
Feng, S., Zou, L., Wang, H., He, R., Liu, K., & Zhu, H. (2018). title. Molecules (Basel, Switzerland) 23.
Xuan, W., Lu, X., Yang, Z., Li, J., Jin, W., & Li, Y. (2022). title. 72, 1797–1808.
Sahinovic, M. M., Struys, M., & Absalom, A. R. (2018). title. Clinical pharmacokinetics 57, 1539–1558.
Yu, S., Xin, W., Jiang, Q., Li, A. title., & BioFactors (2020). (Oxford, England) 46, 934–942.
Hou, Y., Xiao, X., Yu, W., & Qi, S. (2021). title. Journal of immunology research 2021, 4754454.
Yu, W., Gao, D., Jin, W., Liu, S., & Qi, S. (2018). title. Neurochemical research 43, 420–429.
Liang, C., Du, F., Cang, J., & Xue, Z. (2018). title. Journal of anesthesia 32, 62–69.
Hausburg, M. A., Banton, K. L., Roman, P. E., Salgado, F., Baek, P., Waxman, M. J., Tanner, A. 2nd, Yoder, J., & Bar-Or, D. (2020). title. Journal of critical care 56, 281–287.
Han, R. H., Huang, H. M., Han, H., Chen, H., Zeng, F., Xie, X., Liu, D. Y., Cai, Y., Zhang, L. Q., Liu, X., Xia, Z. Y., & Tang, J. (2021). title. Military Medical Research 8, 58.
Chen, L., Heikkinen, L., Wang, C., Yang, Y., Sun, H., & Wong, G. (2019). title. Briefings in bioinformatics 20, 1836–1852.
Wang, M. D., Wang, Y., Xia, Y. P., Dai, J. W., Gao, L., Wang, S. Q., Wang, H. J., Mao, L., Li, M., Yu, S. M., Tu, Y., He, Q. W., Zhang, G. P., Wang, L., Xu, G. Z., Xu, H. B., Zhu, L. Q., & Hu, B. (2016). title. Molecular neurobiology 53, 1310–1321.
Wang, Y., Wang, M. D., Xia, Y. P., Gao, Y., Zhu, Y. Y., Chen, S. C., Mao, L., He, Q. W., Yue, Z. Y., & Hu, B. (2018). title. FASEB journal: official publication of the Federation of American Societies for Experimental Biology 32, 935–944.
Wei, K. C., Chu, P. C., Wang, H. Y., Huang, C. Y., Chen, P. Y., Tsai, H. C., Lu, Y. J., Lee, P. Y., Tseng, I. C., Feng, L. Y., Hsu, P. W., Yen, T. C., & Liu, H. L. (2013). title. PLoS One 8, e58995.
Yu, Z., Lin, L., Jiang, Y., Chin, I., Wang, X., Li, X., Lo, E. H., & Wang, X. (2019). title. Molecular neurobiology 56, 2314–2327.
Chen, W., Ju, X. Z., Lu, Y., Ding, X. W., Miao, C. H., & Chen (2019). J. W. title. 25, 704–713.
Ding, X. W., Sun, X., Shen, X. F., Lu, Y., Wang, J. Q., Sun, Z. R., Miao, C. H., & Chen (2019). J. W. title. Acta pharmacologica Sinica 40, 1303–1313.
Hughes, J. M., Neese, O. R., Bieber, D. D., Lewis, K. A., Ahmadi, L. M., Parsons, D. W., & Canfield, S. G. (2022). title. Frontiers in cellular neuroscience 16, 835649.
Yoon, J. Y., Kim, D. W., Ahn, J. H., Choi, E. J., Kim, Y. H., Jeun, M., & Kim, E. J. (2019). title. 16, 301–309.
Bergmann, S., Lawler, S. E., Qu, Y., Fadzen, C. M., Wolfe, J. M., Regan, M. S., Pentelute, B. L., Agar, N. Y. R., & Cho, C. F. (2018). title. Nature protocols 13, 2827–2843.
Yang, Z., Lin, P., Chen, B., Zhang, X., Xiao, W., Wu, S., Huang, C., Feng, D., Zhang, W., & Zhang, J. (2021). title. Autophagy 17, 3048–3067.
He, J. T., Zhao, X., Xu, L., & Mao, C. Y. (2020). title. Journal of Alzheimer’s disease: JAD 73, 39–58.
Yang, C., Hawkins, K. E., Doré, S., & Candelario-Jalil, E. (2019). title. American journal of physiology. Cell physiology 316, C135-c153.
Nation, D. A., Sweeney, M. D., Montagne, A., Sagare, A. P., D’Orazio, L. M., Pachicano, M., Sepehrband, F., Nelson, A. R., Buennagel, D. P., Harrington, M. G., Benzinger, T. L. S., Fagan, A. M., Ringman, J. M., Schneider, L. S., Morris, J. C., Chui, H. C., Law, M., Toga, A. W., & Zlokovic, B. V. (2019). title. Nature medicine 25, 270–276.
Wang, X., Yu, J. Y., Sun, Y., Wang, H., Shan, H., & Wang, S. (2021). title. International immunopharmacology 96, 107725.
Liu, Y., Wang, L., Du, N., Yin, X., Shao, H., & Yang, L. (2021). title. Inflammation 44, 1750–1761.
Sladojevic, N., Stamatovic, S. M., Johnson, A. M., Choi, J., Hu, A., Dithmer, S., Blasig, I. E., Keep, R. F., & Andjelkovic, A. V. (2019). title. The Journal of neuroscience: the official journal of the Society for Neuroscience 39, 743–757.
Wang, H., Li, T., Zhao, L., Sun, M., Jian, Y., Liu, J., Zhang, Y., Li, Y., Dang, M., & Zhang, G. (2019). title. Journal of molecular neuroscience: MN 68, 295–303.
Wei, C. C., Kong, Y. Y., Hua, X., Li, G. Q., Zheng, S. L., Cheng, M. H., Wang, P., & Miao, C. Y. (2017). title. British journal of pharmacology 174, 3823–3836.
He, S., Guo, Y., Zhao, J., Xu, X., Wang, N., & Liu, Q. (2020). title. Frontiers in pharmacology 11, 376.
Branca, J. J. V., Maresca, M., Morucci, G., Mello, T., Becatti, M., Pazzagli, L., Colzi, I., Gonnelli, C., Carrino, D., Paternostro, F., Nicoletti, C., Ghelardini, C., Gulisano, M., Di Mannelli, C., L. and, & Pacini, A. (2019). title. International journal of molecular sciences 20.
Zhang, T., Wang, Y., Xia, Q., Tu, Z., Sun, J., Jing, Q., Chen, P., & Zhao, X. (2021). title. Frontiers in cell and developmental biology 9, 637233.
Chen, W., Ju, X. Z., Lu, Y., Ding, X. W., Miao, C. H., & Chen (2019). J. W. title. CNS neuroscience & therapeutics 25, 704–713.
Yan, H., Kanki, H., Matsumura, S., Kawano, T., Nishiyama, K., Sugiyama, S., Takemori, H., Mochizuki, H., & Sasaki, T. (2021). title. Cell death discovery 7, 380.
Wu, J., He, J., Tian, X., Luo, Y., Zhong, J., Zhang, H., Li, H., Cen, B., Jiang, T., & Sun, X. (2020). title. Journal of neurochemistry 153, 710–726.
Sui, S., Sun, L., Zhang, W., Li, J., Han, J., Zheng, J., & Xin, H. (2021). title. Cellular and molecular neurobiology 41, 1311–1324.
Liu, D., Liu, F., Wang, X., Qiao, Y., Pan, S., Yang, Y., Hu, Y., Zhang, Y., Tian, F., & Liu, Z. (2018). Title. Cell cycle. (Georgetown Tex), 17, 2484–2495. (PMID: 10.1080/15384101.2018.1542901)

PKJ2018-Y56 Expression and regulation of BBB injury-specific miRNAs in postoperative cognitive dysfunction induced by inhalation anesthesia

Keywords: Blood-brain barrier; ZO-1; miR-130a-5p; propofol

0 (Interleukin-1beta)
0 (Lipopolysaccharides)
0 (MicroRNAs)
0 (MIRN130 microRNA, human)
YI7VU623SF (Propofol)
0 (TJP1 protein, human)
0 (Tjp1 protein, mouse)
0 (Tumor Necrosis Factor-alpha)
0 (Zonula Occludens-1 Protein)

Date Created: 20230809 Date Completed: 20240728 Latest Revision: 20241101

20241101

PMC11281946

10.1007/s12033-023-00835-7

37556107