2022 Fiscal Year Research-status Report
Novel anti-fibrotic properties of heme binding proteins including Neuroglobin, Myoglobin, and Hemoglobin in comparison with Cytoglobin in vitro and in vivo
| Project/Area Number |
22K08083
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| Research Institution | Osaka Metropolitan University |
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Principal Investigator |
LE THITHANHTHUY 大阪公立大学, 大学院医学研究科, 特任講師 (10572175)
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| Project Period (FY) |
2022-04-01 – 2025-03-31
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| Keywords | Globin / Cytoglobin / Neuroglobin / Myoglobin / Hemoglobin / Antioxidant / Anti-fibrosis |
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| Outline of Annual Research Achievements |
We have explored that other heme-binding proteins such as hemoglobin (HB), myoglobin (MB), and neuroglobin (NGB) which also possing the gas binding, and ROS scavenging function, have showed the same anti-fibrotic properties as CYGB. The antioxidant, and ROS scavenging function of human HB, MB, and NGB in comparison with CYGB as well as structure alteration regulating their function have been examined. Intra-cellular and tissue bio-distribution, the kinetics, safety assay, and anti-fibrotic function of these globins were demonstrated both in vitro and in vivo.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
We performed RNA-seq analysis in rhNGB and MB-treated
HHSteCs compared with untreated controls. We investigated the common and differential pathways activated in HHSteCs treated with 4 μM MB or NGB (n = 3,
each group). The RNA-seq data revealed that 2977 and 1637 genes were
significantly changed by 2-fold or greater in the MB and NGB
treatment groups, respectively, compared with untreated controls. RNA-seq analysis revealed the downregulation of ECM-encoding and fibrosis-related genes, and the upregulation of transcription factors that regulate the deactivation phenotype of HHSteCs, including PPARγ, ETS1, ETS2, and Interferon regulatory factor (IRF) 1. These findings were confirmed by quantitative reverse
transcriptase-polymerase chain reaction.
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| Strategy for Future Research Activity |
Determine the specific and common mechanism action of these globins related to their anti-fibrotic activity. We need to explore the common and specific pathways related to anti-inflammation, and anti-fibrosis function of these globins via heatmap analysis, and enrichment analysis, a comprehensive resource for curated gene sets and a search engine that accumulates biological knowledge for further biological discoveries (Enrichr is freely available at: http://amp.pharm.mssm.edu/Enrichr.). Examining the potential specific targets which binding to these globins may induce conformation changes and facilitate their function. Taken together, these data will shed new light on the function and application of CYGB, MB, and NGB in liver diseases.
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| Causes of Carryover |
We need to perform multiple assays for assessing the potential application of rhCYGB and other globins as anti-fibrosis therapy. Safety assays for short-term and long-term treatment of globins, measuring the concentration of globin following in vivo treatment, and side effects of globins will be explored.
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[Journal Article] Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms2022
Author(s)
Truong HH, Sato-Matsubara M, Yuasa H, Matsubara T, Thuy LTT, Ikenaga H, Dong MP, Hanh NV, Hieu VN, Hoang DV, Hai H, Okina Y, Enomoto M, Tamori A, Daikoku A, Urushima H, Kazuo Ikeda, Dat NQ, Yasui Y, Shinkawa H, Kubo S, Yamagishi R, Ohtani N, Yoshizato K, Gracia-Sancho J, Kawada N
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Journal Title
Science Advances
Volume: 8
Pages: eabo5525
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Gasdermin D?mediated release of IL-33 from senescent hepatic stellate cells promotes obesity-associated hepatocellular carcinoma2022
Author(s)
Yamagishi R, Kamachi F, Nakamura M, Yamazaki S, Kamiya T, Takasugi M, Cheng Y, Nonaka Y, Yukawa-Muto Y, Thuy LTT, Harada Y, Arai T, Loo TM, Yoshimoto S, Ando T, Nakajima M, Taguchi H, Ishikawa T, Akiba H, Miyake S, Kubo M, Iwakura Y, Fukuda S, Chen WY, Kawada N, Rudensky A, Nakae S, Hara E, Ohtani N
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Journal Title
Science Immunology
Volume: 7
Pages: eabl7209
DOI
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] 1.Soluble immune checkpoint protein CD27 is a novel prognostic predictor of HCC development in HCV-SVR patients.2022
Author(s)
Thuy LTT (演者名), Dong MP, Hai H, Hieu VN, Dinh VH, Uchida-Kobayashi S, Enomoto M, Ohtani N, Tamori A, Kawada N.
Organizer
第70回米国肝臓学会議（AASLD)、ワシントンDC, 米国
Int'l Joint Research
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