Full metadata record
DC Field | Value | Language |
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dc.contributor.author | 장기석 | - |
dc.date.accessioned | 2022-09-07T01:43:24Z | - |
dc.date.available | 2022-09-07T01:43:24Z | - |
dc.date.issued | 2020-12 | - |
dc.identifier.citation | EMBO MOLECULAR MEDICINE, v. 12, no. 12, article no. e12497, page. 1-17 | en_US |
dc.identifier.issn | 1757-4676 | - |
dc.identifier.issn | 1757-4684 | - |
dc.identifier.uri | https://www.embopress.org/doi/full/10.15252/emmm.202012497 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/172876 | - |
dc.description.abstract | The Rv2626c protein of Mycobacterium tuberculosis is a promising vaccine candidate owing to its strong serum antibody response in patients with tuberculosis. However, there is limited information regarding the intracellular response induced by Rv2626c in macrophages. In this study, we demonstrated that Rv2626c interacts with the RING domain of TRAF6 and inhibits lysine (K) 63-linked polyubiquitination of TRAF6 (E3 ubiquitin ligase activity); this results in the suppression of TLR4 inflammatory signaling in macrophages. Furthermore, we showed that the C-terminal 123-131-amino acid Rv2626c motif promotes macrophage recruitment, phagocytosis, M2 macrophage polarization, and subsequent bacterial clearance. We developed rRv2626c-CA, a conjugated peptide containing the C-terminal 123-131-amino acid Rv2626c that targets macrophages, penetrates the cell membrane, and has demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture-induced sepsis. This multifunctional rRv2626c-CA has considerably improved potency, with an IC50 that is 250-fold (in vitro) or 1,000-fold (in vivo) lower than that of rRv2626c-WT. We provide evidence for new peptide-based drugs with anti-inflammatory and antibacterial properties for the treatment of sepsis. | en_US |
dc.description.sponsorship | This work was supported by the NRF grant funded by the Korea government (MSIP) (2016R1D1A1A02937312 and 2019R1I1A2A01064237); a grant from the KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (HI16C1653). We would like to thank all members of the Infection Biology Lab for critical reading and discussion of the manuscript. | en_US |
dc.language.iso | en | en_US |
dc.publisher | WILEY | en_US |
dc.subject | macrophage-targeting | en_US |
dc.subject | Mycobacterium tuberculosisRv2626cpeptide | en_US |
dc.subject | sepsis | en_US |
dc.subject | TRAF6 | en_US |
dc.title | Mycobacterium tuberculosis Rv2626c-derived peptide as a therapeutic agent for sepsis | en_US |
dc.type | Article | en_US |
dc.relation.no | 12 | - |
dc.relation.volume | 12 | - |
dc.identifier.doi | 10.15252/emmm.202012497 | - |
dc.relation.page | 1-17 | - |
dc.relation.journal | EMBO MOLECULAR MEDICINE | - |
dc.contributor.googleauthor | Kim, Sun Young | - |
dc.contributor.googleauthor | Kim, Donggyu | - |
dc.contributor.googleauthor | Kim, Sojin | - |
dc.contributor.googleauthor | Lee, Daeun | - |
dc.contributor.googleauthor | Mun, Seok-Jun | - |
dc.contributor.googleauthor | Cho, Euni | - |
dc.contributor.googleauthor | Son, Wooic | - |
dc.contributor.googleauthor | Jang, Kiseok | - |
dc.contributor.googleauthor | Yang, Chul-Su | - |
dc.relation.code | 2020048498 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | medartisan | - |
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