東京大学 · 医学
福井教授の研究室は、心血管・腎臓疾患における炎症反応の制御機構に注目し、特に転写因子KLF5が腎疾患や動脈硬化、心不全に及ぼす役割を解明しています。特に、KLF5の発現調節が腎間質障害や血管の石灰化、心不全に伴う全身的炎症反応に与える影響を、マウスモデルを用いて分子機構から機能的意義まで総合的に解析しています。また、リノイック酸受容体を標的にした薬理的介入が疾患の進行を抑制する可能性にも注目しています。
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Renal tubulointerstitial damage is the final common pathway leading from chronic kidney disease to end-stage renal disease. Inflammation is clearly involved in tubulointerstitial injury, but it remains unclear how the inflammatory processes are initiated and regulated. Here, we have shown that in the mouse kidney, the transcription factor Krüppel-like factor-5 (KLF5) is mainly expressed in collecting duct epithelial cells and that Klf5 haploinsufficient mice (Klf5+/- mice) exhibit ameliorated re
The heart is composed of several cell types including cardiomyocytes, cardiac fibroblasts, endothelial, and smooth muscle cells. In addition to these major cell types, cardiac macrophages are also present in small numbers under physiological conditions. Recently, the resident macrophage is considered to have vital functions in the maintenance of tissues and homeostasis in many organs, including brain, liver, adipose tissue, lymphatic tissue, and intestinal tract. However, detailed functions of t
Modulation of smooth muscle cell (SMC) phenotype plays a central role in neointima formation. We recently demonstrated that Am80, a synthetic retinoic acid receptor alpha-specific agonist, inhibits the activity of the transcription factor KLF5, which is essential for neointima formation after vascular injury. In the present study, we aimed to further analyze the mechanism by which Am80 inhibits KLF5 and the effects of inhibiting KLF5 on SMCs and vascular lesion formation, as well as to evaluate
Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dy
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