Phoenix Bio

PXBマウス関連の学術論文(NASH病態モデル動物)のご紹介:株式会社フェニックスバイオ

2021/11/19

弊社研究員(喜早)のPXBマウス関連の学術論文が発表されましたのでご紹介申し上げます。

【詳細】
掲載雑誌名:Biomedicines 2021, 9, 1647. ; https://doi.org/10.3390/biomedicines9111647
論文名:Estimating Drug Efficacy with a Diet-Induced NASH Model in Chimeric Mice with Humanized Livers.
著者:Keishi Kisoh, et. al.(株式会社フェニックスバイオ)

概要:
非アルコール性脂肪性肝疾患/肝炎(NAFLD/NASH)は生活習慣病と密接にかかわる疾患で先進国を中心にその患者数が増加傾向にあり、肝硬変や肝がんの原因となる重大な健康障害の1つです。現在、NASHに対して有用な治療薬は存在せず、多くの製薬会社等でその開発が進められています。今回我々は、東京都医学総合研究所および大阪府済生会吹田病院との共同研究により、ヒト肝細胞キメラマウス(PXBマウス)にコリン欠乏メチオニン減量高脂肪食(CDAHFD)を摂餌することでヒトNASHモデルの作製に成功しました。本モデルは、脂肪肝による肝障害から線維化までの一連のNASH病態を発症するのに加え、バルーニングやマロリーデング小体*といったヒトNASH患者で見られる所見と同様の形態の肝細胞変性を示しておりました。さらに、本モデルにPPARa/d agonistのElafibranorを処置したところ、治験と同様の結果が得られました。以上の内容は、PXBマウスがNASHの病態解明や創薬研究に寄与できることを示す重要な結果であると考えています。

*バルーニング・マロリーデング小体
従来のマウスモデルでは、脂肪化した肝細胞との判別が難しかったがPXBマウスでは判別が容易で病態のマーカーとして評価が可能である。

Bile acid dysmetabolism in the gut-microbiota-liver axis under hepatitis C virus infection

2021/10/12

Inoue, T. Funatsu, Y. Ohnishi, M. Isogawa, M. Kawashima, K. Tanaka, M. Moriya, K. Kawaratani, H. Momoda, R. Iio, E. Nakagawa, H. Suzuki, Y. Matsuura, K. Fujiwara, K. Nakajima, A. Yoshiji, H. Nakayama, J. Tanaka, Y.

Liver Int. 2021 Aug 19. doi: 10.1111/liv.15041.

HBx-induced degradation of Smc5/6 complex impairs homologous recombination-mediated repair of damaged DNA

2021/10/12

Sekiba, K. Otsuka, M. Funato, K. Miyakawa, Y. Tanaka, E. Seimiya, T. Yamagami, M. Tsutsumi, T. Okushin, K. Miyakawa, K. Ryo, A. Koike, K.

J Hepatol. 2021 Aug 25. pii: S0168-8278(21)02005-5. doi: 10.1016/j.jhep.2021.08.010.

Infection courses, virological features and IFN-alpha responses of HBV genotypes in cell culture and animal models

2021/10/12

Zhang, M. Zhang, Z. Imamura, M. Osawa, M. Teraoka, Y. Piotrowski, J. Ishida, Y. Sozzi, V. Revill, P. A. Saito, T. Chayama, K. Liang, T. J.

J Hepatol. 2021 Aug 4. pii: S0168-8278(21)01960-7. doi: 10.1016/j.jhep.2021.07.030.

Chimeric Mouse With Humanized Liver Is an Appropriate Animal Model to Investigate Mode of Action for Porphyria-Mediated Hepatocytotoxicity

2021/10/12

Toxicol Pathol. 2021 Jul 9:1926233211027474. doi: 10.1177/01926233211027474.

Eguchi, A. Fukunaga, S. Ogata, K. Kushida, M. Asano, H. Cohen, S. M. Sukata, T.

Application of humanized mice to toxicology studies: Evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR)

2021/10/12

Journal Toxicologic Pathology 2021; 34(4): 283-297. doi: https://doi.org/10.1293/tox.2021-0027

Tomoya Yamada

 

Critical evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR)

2021/10/12

Yamada, T. Cohen, S. M. Lake, B. G.

Crit Rev Toxicol. 2021;51(5):373-394. doi:10.1080/10408444.2021.1939654. Epub 2021 Jul 15.

Epidermal growth factor receptor is a host-entry cofactor triggering hepatitis B virus internalization

2021/10/12

Iwamoto, M. Saso, W. Sugiyama, R. Ishii, K. Ohki, M. Nagamori, S. Suzuki, R. Aizaki, H. Ryo, A. Yun, J. H. Park, S. Y. Ohtani, N. Muramatsu, M. Iwami, S. Tanaka, Y. Sureau, C. Wakita, T. Watashi, K.
Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8487-8492. doi: 10.1073/pnas.1811064116. Epub 2019 Apr 5.

PXBマウス・PXB-cells関連の学術論文のご紹介:住友化学

2021/08/05

住友化学様より、PXBマウス・PXB-cells関連の学術論文(3報)が発表されましたのでご紹介申し上げます。

【 1 】
掲載雑誌名:Journal of Toxicological Pathology
論文名:Review / Featured Article Application of humanized mice to toxicology studies: evaluation of the human relevance

of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor
(CAR)

著者:Dr. Tomoya Yamada(住友化学株式会社)
URL:https://www.jstage.jst.go.jp/article/tox/advpub/0/advpub_2021-0027/_article/-char/en

【 2 】
掲載雑誌名:Toxicologic Pathology
論文名:Chimeric Mouse With Humanized Liver Is an Appropriate Animal Model to Investigate Mode of Action for

Porphyria-Mediated Hepatocytotoxicity

著者:Dr. Ayumi Eguchi(住友化学株式会社)
URL:https://journals.sagepub.com/eprint/F3WIGCATIMNKMI35FEPH/full

【 3 】
掲載雑誌名:Critical Reviews of Toxicology
論文名:Critical evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of

the constitutive androstane receptor (CAR)

著者:Dr. Tomoya Yamada(住友化学株式会社)
URL:https://www.tandfonline.com/doi/full/10.1080/10408444.2021.1939654

MafF is an antiviral host factor that suppresses transcription from Hepatitis B Virus core promoter

2021/07/09

Marwa K. Ibrahim, Tawfeek H. Abdelhafez, Junko S. Takeuchi, Kosho Wakae, Masaya Sugiyama, Masataka Tsuge, Masahiko Ito, Koichi Watashi, Mohamed El. Kassas, Takanobu Kato, Asako Murayama, Tetsuro Suzuki, Kazuaki Chayama, Kunitada Shimotohno, Masamichi Muramatsu, Hussein H. Aly, Takaji Wakita

J Virol. 2021 Jul 12;95(15): e0076721. doi: 10.1128/JVI.00767-21. Epub 2021 Jul 12.

Cholesterol-binding translocator protein TSPO regulates steatosis and bile acid synthesis in nonalcoholic fatty liver disease

2021/07/09

Li, Y. Chen, L. Li, L. Sottas, C. Petrillo, S. K. Lazaris, A. Metrakos, P. Wu, H. Ishida, Y. Saito, T. Golden-Mason, L. Rosen, H. R. Wolff, J. J. Silvescu, C. I. Garza, S. Cheung, G. Huang, T. Fan, J. Culty, M. Stiles, B. Asahina, K. Papadopoulos, V.

iScience. 2021 May 1;24(5):102457. doi: 10.1016/j.isci.2021.102457.

Loss of lysophosphatidic acid receptor 1 in hepatocytes reduces steatosis via down-regulation of CD36

2021/07/09

Lua, I. Balog, S. Yanagi, A. Tateno, C. Asahina, K.

Prostaglandins Other Lipid Mediat. 2021 Jun 17:106577. doi: 10.1016/j.prostaglandins.2021.106577.

Novel drug resistance-associated substitutions against pibrentasvir emerged in genotype 1b hepatitis C virus-infected human hepatocyte transplanted mice

2021/07/09

Ohya, K. Imamura, M. Teraoka, Y. Uchida, T. Fujino, H. Nakahara, T. Ono, A. Murakami, E. Yamauchi, M. Kawaoka, T. Miki, D. Tsuge, M. Abe-Chayama, H. Hayes, C. N. Aikata, H. Ishida, Y. Tateno, C. Song, H. Miyayama, Y. Hijikata, M. Chayama, K.

Biochem Biophys Res Commun. 2021 Jun 25;559:78-83. doi: 10.1016/j.bbrc.2021.04.062. Epub 2021 Apr 29.

Prediction of human pharmacokinetics for low-clearance compounds using pharmacokinetic data from chimeric mice with humanized livers

2021/07/09

Yoshida, K. Doi, Y. Iwazaki, N. Yasuhara, H. Ikenaga, Y. Shimizu, H. Nakada, T. Watanabe, T. Tateno, C. Sanoh, S.Kotake, Y.

Clin Transl Sci. 2021 Jun 3. doi: 10.1111/cts.13070.

Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system

2021/06/17

Shinohara, M. Arakawa, H. Oda, Y. Shiraki, N. Sugiura, S. Nishiuchi, T. Satoh, T. Iino, K. Leo, S. Kato, Y. Araya, K. Kawanishi, T. Nakatsuji, T. Mitsuta, M. Inamura, K. Goto, T. Shinha, K. Nihei, W.
Sci Rep. 2021 Mar 8;11(1):5437. doi: 10.1038/s41598-021-84861-y.

Geranylgeranylacetone decreases the production of hepatitis B virus-related antigen by comprehensive downregulation of mRNA transcription activity

2021/06/17

Haraguchi, M. Miuma, S. Yamamoto, K. Nakao, Y. Ichikawa, T. Kanda, Y. Sasaki, R. Fukushima, M. Akazawa, Y. Miyaaki, H. Nakao, K.
J Gastroenterol Hepatol. 2021 Jan 4. doi: 10.1111/jgh.15394.

Cell-based high-throughput screening for the evaluation of reactive metabolite formation potential

2021/06/17

Harada, K. Kohara, H. Yukawa, T. Matsumiya, K. Shinozawa, T.
Toxicol In Vitro. 2021 Aug;74:105159. doi: 10.1016/j.tiv.2021.105159. Epub 2021 Apr 3.

Safety and Efficacy of Avaren-Fc Lectibody Targeting HCV High-Mannose Glycans in a Human Liver Chimeric Mouse Model

2021/06/17

Dent, M. Hamorsky, K. Vausselin, T. Dubuisson, J. Miyata, Y. Morikawa, Y. Matoba, N.
Cell Mol Gastroenterol Hepatol. 2021;11(1):185-198. doi: 10.1016/j.jcmgh.2020.08.009. Epub 2020 Aug 27.

Interferon signaling suppresses the unfolded protein response and induces cell death in hepatocytes accumulating hepatitis B surface antigen

2021/06/17

Baudi, I. Isogawa, M. Moalli, F. Onishi, M. Kawashima, K. Ishida, Y. Tateno, C. Sato, Y. Harashima, H. Ito, H. Ishikawa, T. Wakita, T. Iannacone, M. Tanaka, Y.
PLoS Pathog. 2021 May 12;17(5):e1009228. doi: 10.1371/journal.ppat.1009228.

Understanding hepatitis B virus dynamics and the antiviral effect of interferon-alpha treatment in humanized chimeric mice

2021/06/17

Reinharz, V. Ishida, Y. Tsuge, M. Durso-Cain, K. Chung, T. L. Tateno, C. Perelson, A. S. Uprichard, S. L. Chayama, K. Dahari, H.
J Virol. 2021 Apr 28. pii: JVI.00492-20. doi: 10.1128/JVI.00492-20.