Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Akito Tsuruta Last modified date:2023.06.29

Assistant Professor / Department of Pharmaceutical Health Care and Sciences / Faculty of Pharmaceutical Sciences

1. T. Tanaka, Y. Koga, Y. Honda, A. Tsuruta, N. Matsunaga, S. Koyanagi, S. Ohdo, R. Yazaki & T. Ohshima, Ternary catalytic α-deuteration of carboxylic acids, Nature Synthesis, 2022.09.
2. Omata Y, Okawa M, Haraguchi M, Tsuruta A, Matsunaga N, Koyanagi S, Ohdo S., RNA editing enzyme ADAR1 controls miR-381-3p-mediated expression of multidrug resistance protein MRP4 via regulation of circRNA in human renal cells., journal of biological chemistry, 2022.04.
3. Akito Tsuruta, Yuki Shiiba, Naoya Matsunaga, Marina Fujimoto, Yuya Yoshida, Satoru Koyanagi, Shigehiro Ohdo, Diurnal expression of PD-1 on tumor-associated macrophages underlies the dosing time-dependent anti-tumor effects of the PD-1/PD-L1 inhibitor BMS-1 in B16/BL6 melanoma-bearing mice, Molecular cancer research, 2022.02, Cancer cells have acquired several pathways to escape from host immunity in the tumor microenvironment. Programmed death-1 (PD-1) receptor and its ligand PD-L1 are involved in the key pathway of tumor immune escape, and immune checkpoint therapy targeting PD-1 and PD-L1 has been approved for the treatment of patients with certain types of malignancies. Although PD-1 is a well-characterized receptor on T cells, the immune checkpoint receptor is also expressed on tumor-associated macrophages (TAMs), a major immune component of the tumor microenvironment. In this study, we found significant diurnal oscillation in the number of PD-1-expressing TAMs collected from B16/BL6 melanoma-bearing mice. The levels of Pdcd1 mRNA, encoding PD-1, in TAMs also fluctuated in a diurnal manner. Luciferase reporter and bioluminescence imaging analyses revealed that a nuclear factor-kappa B (NF-kB) response element in the upstream region of the Pdcd1 gene is responsible for its diurnal expression. A circadian regulatory component, DEC2, whose expression in TAMs exhibited diurnal oscillation, periodically suppressed NF-kB-induced transactivation of the Pdcd1 gene, resulting in diurnal expression of PD-1 in TAMs. Furthermore, the anti-tumor efficacy of BMS-1, a small molecule inhibitor of PD-1/PD-L1, was enhanced by administering it at the time of day when PD-1 expression increased on TAMs. These findings suggest that identification of the diurnal expression of PD-1 on TAMs is useful for selecting the most appropriate time of day to administer PD-1/PD-L1 inhibitors. Implications: Selecting the most appropriate dosing time of PD-1/PD-L1 inhibitors may aid in developing cancer immunotherapy with higher efficacy..
4. Yuji Omata, Tomoaki Yamauchi, Akito Tsuruta, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo, RNA editing enzyme ADAR1 governs the circadian expression of P-glycoprotein in human renal cells by regulating alternative splicing of the ABCB1 gene, Journal of biological chemistry, 10.1016/j.jbc.2021.100601, 2021.06, The expression and function of some xenobiotic transporters varies according to the time of day, causing the dosing time-dependent changes in drug disposition and toxicity. P-glycoprotein (P-gp), encoded by the ABCB1 gene, is highly expressed in the kidneys and functions in the renal elimination of various drugs. The elimination of several P-gp substrates was demonstrated to vary depending on administration time, but the underlying mechanism remains unclear. We found that adenosine deaminase acting on RNA (ADAR1) was involved in the circadian regulation of P-gp expression in human renal proximal tubular epithelial cells (RPTECs). After synchronization of the cellular circadian clock by dexamethasone treatment, the expression of P-gp exhibited a significant 24-h oscillation in RPTECs, but this oscillation was disrupted by the down- regulation of ADAR1. Although ADAR1 catalyzes adenosine-to-inosine (A-to-I) RNA editing in double-stranded RNA (dsRNA) substrates, no significant ADAR1-regulated editing sites were detected in the human ABCB1 transcripts in RPTECs. On the other hand, down- regulation of ADAR1 induced alternative splicing in intron 27 of the human ABCB1 gene, resulting in the production of retained intron transcripts. The aberrant spliced transcript was sensitive to nonsense- mediated mRNA decay (NMD), leading to the decreased stability of ABCB1 mRNA and prevention of the 24-h oscillation of P-gp expression. These finding support the notion that ADAR1-mediated regulation of alternative splicing of the ABCB1 gene is a key mechanism of circadian expression of P-gp in RPTECs, and the regulatory mechanism may underlie the dosing time-dependent variations in the renal elimination of P-gp substrates..
5. Takashi Ogino, Naoya Matsunaga, Takahiro Tanaka, Tomohito Tanihara, Hideki Terajima, Hikari Yoshitane, Yoshitaka Fukada, Akito Tsuruta, Satoru Koyanagi, Shigehiro Ohdo, Post-transcriptional repression of circadian component CLOCK regulates cancer-stemness in murine breast cancer cells, Elife, 10.7554/eLife.66155, 2021.04, Disruption of the circadian clock machinery in cancer cells is implicated in tumor malignancy. Studies on cancer therapy reveal the presence of heterogeneous cells, including breast cancer stem-like cells (BCSCs), in breast tumors. BCSCs are often characterized by high aldehyde dehydrogenase (ALDH) activity, associated with the malignancy of cancers. In this study, we demonstrated the negative regulation of ALDH activity by the major circadian component CLOCK in murine breast cancer 4T1 cells. The expression of CLOCK was repressed in high-ALDH-activity 4T1, and enhancement of CLOCK expression abrogated their stemness properties, such as tumorigenicity and invasive potential. Furthermore, reduced expression of CLOCK in high-ALDH-activity 4T1 was post-transcriptionally regulated by microRNA: miR-182. Knockout of miR-182 restored the expression of CLOCK, resulted in preventing tumor growth. Our findings suggest that increased expression of CLOCK in BCSCs by targeting post-transcriptional regulation overcame stemness-related malignancy and may be a novel strategy for breast cancer treatments..
6. Yuya Yoshida, Naoya Matsunaga, Takaharu Nakao, Kengo Hamamura, Hideaki Kondo, Tomomi Ide, Hiroyuki Tsutsui, Akito Tsuruta, Masayuki Kurogi, Michio Nakaya, Hitoshi Kurose, Satoru Koyanagi, Shigehiro Ohdo., Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis, Nature communications, 10.1038/s41467-021-23050-x, 2021.05, Dysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure..
7. [Naoki Kusunose,Akito Tsuruta,Kengo Hamamura,Yuya Tsurudome,Yuya Yoshida,Takahiro Akamine,Naoya Matsunaga,Satoru Koyanagi,Shigehiro Ohdo], Circadian expression of Glycoprotein 2 ( Gp2 ) gene is controlled by a molecular clock in mouse Peyer's patches, Genes to cells, 10.1111/gtc.12758, 2020.04.
8. Shohei Uchinomiya,Naoya Matsunaga,Koichiro Kamoda,Ryosuke Kawagoe,Akito Tsuruta,Shigehiro Ohdo,Akio Ojida, Fluorescence detection of metabolic activity of the fatty acid beta oxidation pathway in living cells, Chemical comunications, 10.1039/c9cc09993j, 2020.02.
9. [Hinako Kimura,Naoya Matsunaga,Keisuke Kakimoto,Miyako Watanabe,Akito Tsuruta,Naoki Kusunose,Shoya Shiromizu,Satoru Koyanagi,Shigehiro Ohdo], Epithelial cell adhesion molecule expression in hepatic stem/progenitor cells is controlled by the molecular clock system, Biochemical and biophysical research communications, 10.1016/j.bbrc.2018.06.117, 2018.09.
10. Fumiyasu Okazaki,Naoya Matsunaga,Hiroyuki Okazaki,Hiroki Azuma,Kengo Hamamura,Akito Tsuruta,Yuya Tsurudome,Takashi Ogino,Yukinori Hara,Takuya Suzuki,Kenji Hyodo,Hiroshi Ishihara,Hiroshi Kikuchi,Hideto To,Hironori Aramaki,Satoru Koyanagi,Shigehiro Ohdo, Circadian Clock in a Mouse Colon Tumor Regulates Intracellular Iron Levels to Promote Tumor Progression, Journal of biological chemistry, 10.1074/jbc.m115.713412, 2016.03.
11. [Naoya Matsunaga,Eriko Ikeda,Keisuke Kakimoto,Miyako Watanabe,Naoya Shindo,Akito Tsuruta,Hisako Ikeyama,Kengo Hamamura,Kazuhiro Higashi,Tomohiro Yamashita,Hideaki Kondo,Yuya Yoshida,Masaki Matsuda,Takashi Ogino,Kazutaka Tokushige,Kazufumi Itcho,Yoko Furuichi,Takaharu Nakao,Kaori Yasuda,Atsushi Doi,Toshiaki Amamoto,Hironori Aramaki,Makoto Tsuda,Kazuhide Inoue,Akio Ojida,Satoru Koyanagi,Shigehiro Ohdo], Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease, EBioMedicine, 10.1016/j.ebiom.2016.10.008, 2016.11.