徳島大学大学院医歯薬学研究部 医学域 医科学部門 生理系 薬理学分野
Department of Pharmacology, Tokushima University Graduate School of of Biomedical Sciences
Research Themes
We're currently promoting the following research themes.
（１）Research on the pathophysiological significance of iron
The analysis of iron metabolism changes in disease states and iron-regulated treatment in animal models has revealed that iron-depleting drugs promote angiogenesis (Ikeda, et al. Atherosclerosis. 2011), suppress oxidative stress and have anti-obesity and anti-diabetic effects (Tajima and Ikeda, et al. Am J Physiol Endocrinol Metab. 2012), and have anti-kidney fibrosis effects (Ikeda and Ozono, et al. PlosOne 2014). Physiol Endocrinol Metab. 2012), anti-renal fibrosis (Ikeda and Ozono, et al. PlosOne 2014), diabetic kidney disease due to dietary iron restriction (Ikeda and Enomoto, et al. Am J Physiol Renal Physiol 2013) and protein-loaded renal interstitial disorders (Ikeda, et al. Sci Rep 2017). Involved in iron oxidative stress-HIF-2α-mediated regulation of erythropoietin expression (Oshima and Ikeda, et al. Lab Invest. 2017), promotion of skeletal muscle degradation by iron excess (Ikeda and Imao, et al. J Trace Elem Med Biol. 2016) and differentiation inhibition (Ikeda and Satoh, et al. FASEB J. 2019) molecular mechanisms. We also reported that macrophage-derived iron stress plays a major role in the development and progression of obesity and diabetes (Ikeda and Watanabe, et al. Diabetologia. 2020). We found that ferrotosis is involved in cisplatin kidney injury (Ikeda, et al. J Trace Elem Med Biol. 2021).
・Research on iron (1, 2)
・Research on epigenetic control mechanisms (3)
・Research on Wakan-yaku (4)
・Iron Metabolic Transformation in Low Gravity Environment (5)
（２）Research on regulatory mechanisms of iron metabolism
Using various pathological models of female postmenopause, chronic kidney disease, and hypertension, the female hormone estrogen (Ikeda, et al. PlosOne 2012), urinary toxins (Hamano and Ikeda, et al. Ikeda, et al. Nephrol Dial Transplant. 2018) angiotensin II (Tajima, et al. Eur J Nutr. 2015) cause ectopic iron accumulation by causing changes in systemic iron metabolism via hepatic hepcidin regulation. Gastric acid secretion inhibitor proton pump inhibitors cause iron deficiency, and the mechanism of iron deficiency was shown to suppress gastrointestinal iron absorption by increasing hepcidin production (Hamano and Ikeda, et al. Tocixol lett. 2020).
（５）Iron Metabolic Transformation in Low Gravity Environment
来たるべき宇宙時代において、微小重力，低重力の環境における生体恒常性変化を解明することが必須である。鉄は必須微量金属元素であるが、宇宙環境では貧血や宇宙放射線などによる鉄が触媒する酸化ストレスが増悪するといわれている。そのため、NASAでは鉄摂取量を定めている。
JAXAマウスサンプルシェアに採択され、低呪力環境におかれたマウスの消化管、胸骨肋骨を用いて、消化管鉄吸収の変化について解析を行っている（投稿中）。この研究で得られた結果から、寝たきり状態における病態解析への応用が期待できる。
（3）Epigenetic Regulatory Mechanisms in Heart Disease
Heart failure is the final manifestation of all cardiac diseases, and the number of heart failure patients is expected to increase as the population ages. Post-translational modifications of histones, the major proteins that make up chromatin, play important roles in a variety of biological processes. In cardiac disease, the transition from cardiac hypertrophy to heart failure is accompanied by a transition in the site of acetylation from the tail domain to the globular domain of histones (Funamoto M et al. Int J Mol Sci 2021). We hypothesize that post-translational modification of histones is important as a transition switch from cardiac hypertrophy to heart failure, and we are now analyzing this hypothesis.
（４）Research on novel actions and molecular mechanisms of Wakan-yaku (Chinese herbal medicines and crude drugs)
Traditional Japanese medicine, Kampo, has developed uniquely based on Chinese medicine to suit the climate and climate of Japan and the constitution of the Japanese people. Herbal medicine plays an important role in Chinese medicine. Based on the concept of using Chinese herbal medicine to enhance the natural healing power of humans, prescriptions are created by combining herbal medicines according to symptoms based on accumulated empirical rules. Combinations of multiple herbal medicines can enhance the efficacy or suppress the toxicity of a given herbal medicine, resulting in significant changes in efficacy and safety. However, there is currently a lack of scientific evidence. In this research project, we will clarify the new effects and molecular mechanisms of Chinese herbal medicine using various disease models, and accumulate basic knowledge that will lead to building evidence for Chinese herbal medicine. Seiryuto, which is used for respiratory diseases, can alleviate cisplatin-induced kidney damage by suppressing inflammation and oxidative stress, and it has been revealed that this effect is due to bamboo boiling, one of the constituent herbal ingredients (Ikeda , et al. Phytomedicine. 2022). It was also found that goreisan, which has a body water regulating effect, suppresses inflammation and oxidative stress, and suppresses chronic kidney disease (Suenaga and Ikeda, et al. J Pharmacol Sci. 2023).