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SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression

Hashimoto, Rina Takahashi, Junya Shirakura, Keisuke Funatsu, Risa Kosugi, Kaori Deguchi, Sayaka Yamamoto, Masaki Tsunoda, Yugo Morita, Maaya Muraoka, Kosuke Tanaka, Masato Kanbara, Tomoaki Tanaka, Shota Tamiya, Shigeyuki Tokunoh, Nagisa Kawai, Atsushi Ikawa, Masahito Ono, Chikako Tachibana, Keisuke Kondoh, Masuo Obana, Masanori Matsuura, Yoshiharu Ohsumi, Akihiro Noda, Takeshi Yamamoto, Takuya Yoshioka, Yasuo Torisawa, Yu-suke Date, Hiroshi Fujio, Yasushi Nagao, Miki Takayama, Kazuo Okada, Yoshiaki 京都大学 DOI:10.1126/sciadv.abo6783

2022.09

概要

In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin–mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2–induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2–induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19.

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参考文献

1. N. Zhu, W. Wang, Z. Liu, C. Liang, W. Wang, F. Ye, B. Huang, L. Zhao, H. Wang, W. Zhou, Y. Deng, L. Mao, C. Su, G. Qiang, T. Jiang, J. Zhao, G. Wu, J. Song, W. Tan, Morphogenesis and cytopathic effect of SARS-CoV-2 infection in human airway epithelial cells. Nat. Commun. 11, 3910 (2020).

2. J. Nascimento Conde, W. R. Schutt, E. E. Gorbunova, E. R. Mackow, Recombinant ACE2 expression is required for SARS-CoV-2 to infect primary human endothelial cells and induce inflammatory and procoagulative responses. MBio 11, e03185-20 (2020).

3. Z. Varga, A. J. Flammer, P. Steiger, M. Haberecker, R. Andermatt, A. S. Zinkernagel, M. R. Mehra, R. A. Schuepbach, F. Ruschitzka, H. Moch, Endothelial cell infection and endotheliitis in COVID-19. Lancet 395, 1417–1418 (2020).

4. Y. Jin, W. Ji, H. Yang, S. Chen, W. Zhang, G. Duan, Endothelial activation and dysfunction in COVID-19: From basic mechanisms to potential therapeutic approaches. Signal Transduct. Target. Ther. 5, 293 (2020).

5. E. Dejana, F. Orsenigo, M. G. Lampugnani, The role of adherens junctions and VE-cadherin in the control of vascular permeability. J. Cell Sci. 121, 2115–2122 (2008).

6. C. Cerutti, A. J. Ridley, Endothelial cell-cell adhesion and signaling. Exp. Cell Res. 358, 31–38 (2017).

7. M. Corada, M. Mariotti, G. Thurston, K. Smith, R. Kunkel, M. Brockhaus, M. G. Lampugnani, I. Martin-Padura, A. Stoppacciaro, L. Ruco, D. M. McDonald, P. A. Ward, E. Dejana, Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc. Natl. Acad. Sci. U.S.A. 96, 9815–9820 (1999).

8. T. Nitta, M. Hata, S. Gotoh, Y. Seo, H. Sasaki, N. Hashimoto, M. Furuse, S. Tsukita, Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J. Cell Biol. 161, 653–660 (2003).

9. Y. Jin, H. Yang, W. Ji, W. Wu, S. Chen, W. Zhang, G. Duan, Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 12, (2020).

10. L. A. Teuwen, V. Geldhof, A. Pasut, P. Carmeliet, COVID-19: The vasculature unleashed. Nat. Rev. Immunol. 20, 389–391 (2020).

11. J. S. Pober, W. C. Sessa, Evolving functions of endothelial cells in inflammation. Nat. Rev. Immunol. 7, 803–815 (2007).

12. J. Liu, Y. Li, Q. Liu, Q. Yao, X. Wang, H. Zhang, R. Chen, L. Ren, J. Min, F. Deng, B. Yan, L. Liu, Z. Hu, M. Wang, Y. Zhou, SARS-CoV-2 cell tropism and multiorgan infection. Cell Discov. 7, 17 (2021).

13. R. M. Cox, J. D. Wolf, R. K. Plemper, Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat. Microbiol. 6, 11–18 (2021).

14. L. Si, H. Bai, M. Rodas, W. Cao, C. Y. Oh, A. Jiang, R. Moller, D. Hoagland, K. Oishi, S. Horiuchi, S. Uhl, D. Blanco-Melo, R. A. Albrecht, W. C. Liu, T. Jordan, B. E. Nilsson-Payant, I. Golynker, J. Frere, J. Logue, R. Haupt, M. McGrath, S. Weston, T. Zhang, R. Plebani, M. Soong, A. Nurani, S. M. Kim, D. Y. Zhu, K. H. Benam, G. Goyal, S. E. Gilpin, R. Prantil-Baun, S. P. Gygi, R. K. Powers, K. E. Carlson, M. Frieman, B. R. tenOever, D. E. Ingber, A human- airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics. Nat. Biomed. Eng. 5, 815–829 (2021).

15. K. H. Benam, R. Villenave, C. Lucchesi, A. Varone, C. Hubeau, H. H. Lee, S. E. Alves, M. Salmon, T. C. Ferrante, J. C. Weaver, A. Bahinski, G. A. Hamilton, D. E. Ingber, Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat. Methods 13, 151–157 (2016).

16. Y. Hashimoto, K. Shirakura, Y. Okada, H. Takeda, K. Endo, M. Tamura, A. Watari, Y. Sadamura, T. Sawasaki, T. Doi, K. Yagi, M. Kondoh, Claudin-5-binders enhance permeation of solutes across the blood-brain barrier in a mammalian model. J. Pharmacol. Exp. Ther. 363, 275–283 (2017).

17. K. Tachibana, Y. Hashimoto, K. Shirakura, Y. Okada, R. Hirayama, Y. Iwashita, I. Nishino, Y. Ago, H. Takeda, H. Kuniyasu, M. Kondoh, Safety and efficacy of an anti-claudin-5 monoclonal antibody to increase blood-brain barrier permeability for drug delivery to the brain in a non-human primate. J. Control. Release 336, 105–111 (2021).

18. A. Taddei, C. Giampietro, A. Conti, F. Orsenigo, F. Breviario, V. Pirazzoli, M. Potente, C. Daly, S. Dimmeler, E. Dejana, Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat. Cell Biol. 10, 923–934 (2008).

19. A. Gupta, M. V. Madhavan, T. J. Poterucha, E. M. DeFilippis, J. A. Hennessey, B. Redfors, C. Eckhardt, B. Bikdeli, J. Platt, A. Nalbandian, P. Elias, M. J. Cummings, S. N. Nouri, M. Lawlor, L. S. Ranard, J. Li, C. Boyle, R. Givens, D. Brodie, H. M. Krumholz, G. W. Stone, S. S. Sethi, D. Burkhoff, N. Uriel, A. Schwartz, M. B. Leon, A. J. Kirtane, E. Y. Wan, S. A. Parikh, Association between antecedent statin use and decreased mortality in hospitalized patients with COVID-19. Nat. Commun. 12, 1325 (2021).

20. W. Chen, R. Sharma, A. N. Rizzo, J. H. Siegler, J. G. Garcia, J. R. Jacobson, Role of claudin-5 in the attenuation of murine acute lung injury by simvastatin. Am. J. Respir. Cell Mol. Biol. 50, 328–336 (2014).

21. A. Ohsumi, J. Takamatsu, I. Yuasa, S. Tanaka, Y. Yutaka, M. Hamaji, D. Nakajima, K. Yamazaki, M. Nagao, H. Date, Living-donor lung transplantation for dyskeratosis congenita. Ann. Thorac. Surg. 112, e397–e402 (2021).

22. S. Torices, R. Cabrera, M. Stangis, O. Naranjo, N. Fattakhov, T. Teglas, D. Adesse, M. Toborek, Expression of SARS-CoV-2-related receptors in cells of the neurovascular unit: Implications for HIV-1 infection. J. Neuroinflammation 18, 167 (2021).

23. J. L. Reynolds, S. D. Mahajan, SARS-COV2 alters blood brain barrier integrity contributing to neuro-inflammation. J. Neuroimmune Pharmacol. 16, 4–6 (2021).

24. L. Zhang, L. Zhou, L. Bao, J. Liu, H. Zhu, Q. Lv, R. Liu, W. Chen, W. Tong, Q. Wei, Y. Xu, W. Deng, H. Gao, J. Xue, Z. Song, P. Yu, Y. Han, Y. Zhang, X. Sun, X. Yu, C. Qin, SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration. Signal Transduct. Target. Ther. 6, 337 (2021).

25. A. Flores-Pliego, J. Miranda, S. Vega-Torreblanca, Y. Valdespino-Vazquez, C. Helguera-Repetto, A. Espejel-Nunez, H. Borboa-Olivares, Y. S. S. Espino, P. Mateu-Rogell, M. Leon-Juarez, V. Ramirez-Santes, A. Cardona-Perez, I. Villegas-Mota, J. Torres-Torres, A. Juarez-Reyes, T. Rizo-Pica, R. O. Gonzalez, L. Gonzalez-Mariscal, G. Estrada-Gutierrez, Molecular insights into the thrombotic and microvascular injury in placental endothelium of women with mild or severe COVID-19. Cell 10, 364 (2021).

26. H. Sirotkin, B. Morrow, B. Saint-Jore, A. Puech, R. Das Gupta, S. R. Patanjali, A. Skoultchi, S. M. Weissman, R. Kucherlapati, Identification, characterization, and precise mapping of a human gene encoding a novel membrane-spanning protein from the 22q11 region deleted in velo-cardio-facial syndrome. Genomics 42, 245–251 (1997).

27. C. Greene, J. Kealy, M. M. Humphries, Y. Gong, J. Hou, N. Hudson, L. M. Cassidy, R. Martiniano, V. Shashi, S. R. Hooper, G. A. Grant, P. F. Kenna, K. Norris, C. K. Callaghan, M. D. Islam, S. M. O'Mara, Z. Najda, S. G. Campbell, J. S. Pachter, J. Thomas, N. M. Williams, P. Humphries, K. C. Murphy, M. Campbell, Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia. Mol. Psychiatry 23, 2156–2166 (2018).

28. K. Morita, H. Sasaki, M. Furuse, S. Tsukita, Endothelial claudin: Claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J. Cell Biol. 147, 185–194 (1999).

29. M. Frye, M. Dierkes, V. Kuppers, M. Vockel, J. Tomm, D. Zeuschner, J. Rossaint, A. Zarbock, G. Y. Koh, K. Peters, A. F. Nottebaum, D. Vestweber, Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin. J. Exp. Med. 212, 2267–2287 (2015).

30. C. N. Duong, A. F. Nottebaum, S. Butz, S. Volkery, D. Zeuschner, M. Stehling, D. Vestweber, Interference with ESAM (endothelial cell-selective adhesion molecule) plus vascular endothelial-cadherin causes immediate lethality and lung-specific blood coagulation. Arterioscler. Thromb. Vasc. Biol. 40, 378–393 (2020).

31. W. Tian, N. Zhang, R. Jin, Y. Feng, S. Wang, S. Gao, R. Gao, G. Wu, D. Tian, W. Tan, Y. Chen, G. F. Gao, C. C. L. Wong, Immune suppression in the early stage of COVID-19 disease. Nat. Commun. 11, 5859 (2020).

32. F. J. Zapatero-Belinchon, R. Moeller, L. Lasswitz, M. van Ham, M. Becker, G. Brogden, E. Rosendal, W. Bi, B. Carriqui-Madronal, K. Islam, A. Lenman, A. P. Gunesch, J. Kirui, T. Pietschmann, A. K. Overby, L. Jansch, G. Gerold, Fluvastatin mitigates SARS-CoV-2 infection in human lung cells. iScience 24, 103469 (2021).

33. M. S. Yang, B. K. Oh, D. Yang, E. Y. Oh, Y. Kim, K. W. Kang, C. W. Lim, G. Y. Koh, S. M. Lee, B. Kim, Ultra- and micro-structural changes of respiratory tracts in SARS-CoV-2 infected Syrian hamsters. Vet. Res. 52, 121 (2021).

34. S. Matsuyama, N. Nao, K. Shirato, M. Kawase, S. Saito, I. Takayama, N. Nagata, T. Sekizuka, H. Katoh, F. Kato, Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc. Natl. Acad. Sci. U.S.A. 117, 7001–7003 (2020).

35. E. Sano, T. Suzuki, R. Hashimoto, Y. Itoh, A. Sakamoto, Y. Sakai, A. Saito, D. Okuzaki, D. Motooka, Y. Muramoto, T. Noda, T. Takasaki, J. I. Sakuragi, S. Minami, T. Kobayashi, T. Yamamoto, Y. Matsumura, M. Nagao, T. Okamoto, K. Takayama, Cell response analysis in SARS-CoV-2 infected bronchial organoids. Commun. Biol. 5, 516 (2022).

36. S. Deguchi, M. Tsuda, K. Kosugi, A. Sakamoto, N. Mimura, R. Negoro, E. Sano, T. Nobe, K. Maeda, H. Kusuhara, H. Mizuguchi, F. Yamashita, Y. S. Torisawa, K. Takayama, Usability of polydimethylsiloxane-based microfluidic devices in pharmaceutical research using human hepatocytes. ACS Biomater Sci. Eng. 7, 3648–3657 (2021).

37. A. Kechin, U. Boyarskikh, A. Kel, M. Filipenko, cutPrimers: A new tool for accurate cutting of primers from reads of targeted next generation sequencing. J. Comput. Biol. 24, 1138–1143 (2017).

38. A. Dobin, C. A. Davis, F. Schlesinger, J. Drenkow, C. Zaleski, S. Jha, P. Batut, M. Chaisson, T. R. Gingeras, STAR: Ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).

39. A. Frankish, M. Diekhans, A. M. Ferreira, R. Johnson, I. Jungreis, J. Loveland, J. M. Mudge, C. Sisu, J. Wright, J. Armstrong, I. Barnes, A. Berry, A. Bignell, S. Carbonell Sala, J. Chrast, F. Cunningham, T. Di Domenico, S. Donaldson, I. T. Fiddes, C. Garcia Giron, J. M. Gonzalez, T. Grego, M. Hardy, T. Hourlier, T. Hunt, O. G. Izuogu, J. Lagarde, F. J. Martin, L. Martinez, S. Mohanan, P. Muir, F. C. P. Navarro, A. Parker, B. Pei, F. Pozo, M. Ruffier, B. M. Schmitt, E. Stapleton, M. M. Suner, I. Sycheva, B. Uszczynska-Ratajczak, J. Xu, A. Yates, D. Zerbino, Y. Zhang, B. Aken, J. S. Choudhary, M. Gerstein, R. Guigo, T. J. P. Hubbard, M. Kellis, B. Paten, A. Reymond, M. L. Tress, P. Flicek, GENCODE reference annotation for the human and mouse genomes. Nucleic Acids Res. 47, D766–D773 (2019).

40. S. Anders, P. T. Pyl, W. Huber, HTSeq—A Python framework to work with high- throughput sequencing data. Bioinformatics 31, 166–169 (2015).

41. M. I. Love, W. Huber, S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).

42. K. Ishida, H. Xu, N. Sasakawa, M. S. Y. Lung, J. A. Kudryashev, P. Gee, A. Hotta, Site-specific randomization of the endogenous genome by a regulatable CRISPR-Cas9 piggyBac system in human cells. Sci. Rep. 8, 310 (2018).

43. E. Sano, S. Deguchi, A. Sakamoto, N. Mimura, A. Hirabayashi, Y. Muramoto, T. Noda, T. Yamamoto, K. Takayama, Modeling SARS-CoV-2 infection and its individual differences with ACE2-expressing human iPS cells. iScience 24, 102428 (2021).

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