研究部門research department

研究概要 Outline

私共は現在下記における細胞老化と腎線維化や筋萎縮との関連を検討しています。

We currently investigate the association of cellular senescence with kidney fibrosis and muscle atrophy especially in these conditions:

・High-fat diet-induced CKD

・Uremic sarcopenia

現況 Current status

高脂肪食は腎障害を惹起し、腎臓尿細管・間質の線維化が観察されます。一方、加齢による骨格筋量および筋力の低下(サルコペニア)は腎不全や尿毒素によっても誘導されることが知られています。両者の成因として酸化ストレスが関与しており、加齢を含めた機序の解明や新規治療の開発に向けて取り組んでいます。

High-fat diet induces kidney injury, where fibrosis is observed in the renal tubules and interstitium. On the other hand, age-related loss of muscle mass and strength (sarcopenia) is induced by kidney failure and uremic toxins. Reactive oxidative stress is involved in the pathophysiology of these situations. We focus on the mechanism including ageing and novel therapy.

これまでとこれから Our history and future

これまで骨代謝、血管石灰化や動脈硬化の進展に取り組み、健診コホートにて咀嚼力と疾患・予後との関連や筋代謝マーカーの研究を進めてきました。今後は、ヒト検体の統合的バンク化を構想しています。

My background is in bone and mineral metabolism, vascular calcification, and atherosclerosis. We are greatly progressing the cohort study regarding masticatory function and muscle metabolism.

In the future, we are planning to make an integrated bank of human samples for researchers at IKRA and Shimane Univ.

共同研究 Collaboration

研究業績 Publications

1. Yano S, Sugimoto T, Tsukamoto T, Chihara K, Kobayashi A, Kitazawa S, Maeda S, Kitazawa R: Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism. Kidney Int 58: 1980-1986, 2000
2. Yano S, Yamaguchi T, Kanazawa I, Ogawa N, Hayashi K, Yamauchi M, Sugimoto T: Uraemic toxin, phenylacetic acid, inhibits osteoblastic proliferation and differentiation: an implication for the pathogenesis of low turnover bone in chronic renal failure. Nephrol Dial Transplant 22: 3160-3165, 2007
3. Notsu Y, Yano S, Shibata H, Nagai A, Nabika T: Plasma arginine/ADMA ratio as a sensitive risk marker for atherosclerosis: Shimane CoHRE Study. Atherosclerosis 239: 61-66,2014
4. Yano S, Nagai A, Isomura M, Yamasaki M, Kijima T, Takeda M, Hamano T, Nabika T: Relationship between blood myostatin levels and kidney function: Shimane CoHRE Study.PLoS One 10: e0141035, 2015
5. Koike S, Yano S, Tanaka S, Sheikh AM, Nagai A, Sugimoto T: Advanced glycation end-products induce apoptosis of vascular smooth muscle cells: a mechanism for vascular calcification. Int J Mol Sci 17: 1567, 2016
6. J-DAVID Investigators, Shoji T, Inaba M, Fukagawa M, Ando R, Emoto M, Fujii H, Fujimori A, Fukui M, Hase H, Hashimoto T, Hirakata H, Honda H, Hosoya T, Ikari Y, Inaguma D,Inoue T, Isaka Y, Iseki K, Ishimura E, Itami N, Ito C, Kakuta T, Kawai T, Kawanishi H, Kobayashi S, Kumagai J, Maekawa K, Masakane I, Minakuchi J, Mitsuiki K, Mizuguchi T,Morimoto S, Murohara T, Nakatani T, Negi S, Nishi S, Nishikawa M, Ogawa T, Ohta K, Ohtake T, Okamura M, Okuno S, Shigematsu T, Sugimoto T, Suzuki M, Tahara H, Takemoto Y, Tanaka K, Tominaga Y, Tsubakihara Y, Tsujimoto Y, Tsuruya K, Ueda S, Watanabe Y, Yamagata K, Yamakawa T, Yano S, Yokoyama K, Yorioka N, Yoshiyama M, Nishizawa Y: Effect of oral alfacalcidol on clinical outcomes in patients without secondary hyperparathyroidism receiving maintenance hemodialysis: The J-DAVID randomized clinical trial. JAMA 320: 2325-2334, 2018
7. Sheikh AM, Yano S, Tabassum S, Omura K, Araki A, Mitaki S, Ito Y, Huang S, Nagai A: Alteration of neural stem cell functions in Ataxia and Male Sterility mice: a possible role of β-tubulin glutamylation in neurodegeneration. Cells 10(1): 155, 2021
8. Tominaga N, Yonaha T, Yamanouchi M, Sumi H, Taki Y, Shibagaki Y, Shiizaki K, Yano S: Bone responsiveness to parathyroid hormone is negatively associated with parathyroid hormone-lowering drug use in patients undergoing hemodialysis: a cross-sectional study. BMC Nephrology 22: 275, 2021
9. Tominaga K, Abe T, Ando Y, Hamano T, Isomura M, Nabika T, Yano S: Changes in masticatory performance and the new onset of diabetes mellitus in older adults: a 5-year longitudinal study. Diabetol Int 14: 165-171, 2022
10. Bhuiya J, Notsu Y, Kobayashi H, Shibly AZ, Sheikh AM, Okazaki R, Yamaguchi K, Nagai A, Nabika T, Abe T, Yamasaki M, Isomura M, Yano S: Neither trimethylamine-N-oxide nor trimethyllysine is associated with atherosclerosis: a cross-sectional study in older Japanese adults. Nutrients 15: 759, 2023
11. Zhang Y, Sheikh AM, Tabassum S, Iwasa K, Shibly AZ, Zhou X, Wang R, Bhuiya J, Abdullah FB, Yano S, Aoki Y, Nagai A: Effect of high-fat diet on cerebral pathological changes of cerebral small vessel disease in SHR/SP rats. Geroscience 2024. In press.