Research and Education

Basic Research

The Basic Research Group conducts world-leading, highly original research by applying new research methods based on molecular biology, physiology, biochemistry, and molecular genetics to solve clinical questions. In particular, we encourage translational research that aims to develop therapeutic methods based on findings from the elucidation of the pathophysiology of cardiovascular diseases. We are widely looking for enthusiastic young researchers and researchers from different fields to join us.

Clinical Research

The Clinical Research Group promotes evidence-based medicine through clinical research in cardiology. In collaboration with many affiliated hospitals, clinical research such as multicenter randomized controlled trials are underway. We also offer courses for young physicians to learn in depth about research design and statistical methods.

Fig.1: Treatment of nonalcoholic steatohepatitis by suppression of miR-33b

Hepatocytes and hepatic stellate cells express more miR-33b than miR-33a, and administration of anti-miR-33b increased ABCA1 expression in hepatocytes and hepatic stellate cells, and through reduction of free cholesterol in these cells and cholesterol crystal in the liver, inflammatory responses and fibrosis in the liver were decreased. Therefore, miR-33b in hepatocytes and hepatic stellate cells is important in the development of NASH, and suppression of miR-33b could be a novel NASH therapy.

Fig.2: Regulation of Adaptive Heat Production by miR-33

Mice deficient in miR-33 are unable to maintain body temperature at low temperatures. We found that this is due to the inability of heat production from brown adipose tissue to occur. In particular, knockdown experiments of catecholamine-producing cell (sympathetic nerve) specific Gabrb2 and Gabra4 demonstrated that miR-33 deficiency enhances inhibitory GABAergic signaling through increased expression of the target gene GABAA receptor subtypes (Gabrb2 and Gabra4). Since cold stimuli increase miR-33 expression in the hypothalamus, miR-33 may act as a switch that enhances the degree of sympathetic activity in the hypothalamus, increasing heat production (adaptive heat production).

Recent Publications

1. Miyagawa S, Horie T, Nishino T, Koyama S, Watanabe T, Baba O, Yamasaki T, Sowa N, Otani C, Matsushita K, Kojima H, Kimura M, Nakashima Y, Obika S, Kasahara Y, Kotera J, Oka K, Fujita R, Sasaki T, Takemiya A, Hasegawa K, Kimura T, Ono K. Inhibition of microRNA-33b in humanized mice ameliorates nonalcoholic steatohepatitis. Life Sci Alliance. 2023 Jun 1;6(8):e202301902. doi: 10.26508/lsa.202301902. PMID: 37263777; PMCID: PMC10235800.
2. Horie T, Nakao T, Miyasaka Y, Nishino T, Matsumura S, Nakazeki F, Ide Y, Kimura M, Tsuji S, Rodriguez RR, Watanabe T, Yamasaki T, Xu S, Otani C, Miyagawa S, Matsushita K, Sowa N, Omori A, Tanaka J, Nishimura C, Nishiga M, Kuwabara Y, Baba O, Watanabe S, Nishi H, Nakashima Y, Picciotto MR, Inoue H, Watanabe D, Nakamura K, Sasaki T, Kimura T, Ono K. microRNA-33 maintains adaptive thermogenesis via enhanced sympathetic nerve activity. Nat Commun. 2021 Feb 16;12(1):843. doi: 10.1038/s41467-021-21107-5. PMID: 33594062; PMCID: PMC7886914.
3. Kuwabara Y, Tsuji S, Nishiga M, Izuhara M, Ito S, Nagao K, Horie T, Watanabe S, Koyama S, Kiryu H, Nakashima Y, Baba O, Nakao T, Nishino T, Sowa N, Miyasaka Y, Hatani T, Ide Y, Nakazeki F, Kimura M, Yoshida Y, Inada T, Kimura T, Ono K. Lionheart LincRNA alleviates cardiac systolic dysfunction under pressure overload. Commun Biol. 2020 Aug 13;3(1):434. doi: 10.1038/s42003-020-01164-0. PMID: 32792557; PMCID: PMC7426859.
4. Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, Nakazeki F, Ide Y, Koyama S, Kimura M, Hanada R, Nakamura T, Inada T, Hasegawa K, Conway SJ, Kita T, Kimura T, Ono K. MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol. Circ Res. 2017 Mar 3;120(5):835-847. doi: 10.1161/CIRCRESAHA.116.309528. Epub 2016 Dec 5. PMID: 27920122.
5. Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Matsumura S, Inoue K, Marusawa H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K. MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice. Nat Commun. 2013;4:2883. doi: 10.1038/ncomms3883. PMID: 24300912; PMCID: PMC3863899.

Laboratory

Staff Members

Professor：Koh Ono
Senior Lecturer︓Satoshi Shizuta, Takahiro Horie
Assistant Professor︓ Shin Watanabe, Kyohei Yamaji, Hiroki Shiomi ,Yugo Yamashita
Assistant Professor (Hospital)︓ Kenji Nakastuma
Assistant Professor (Hospital – Clinical Laboratory)︓Shushi Nishiwaki

Funded Laboratory

iACT

Himedic Ward

TEL：+81-75-751-4254
FAX：+81-75-751-3289
e-mail：junkan@kuhp.kyoto-u.ac.jp
URL：http://kyoto-u-cardio.jp/