Tohoku University · Medicine
노리오 스즈끼 교수의 연구실은 신장에서의 에리스포이에틴(Epo) 조절 메커니즘과 그 기능을 중심으로, 비혈액세포적 기능을 포함한 Epo-EpoR 시스템의 다각적 역할을 규명하고 있습니다. 특히 신장 내 Epo 생성 세포(REPs)가 저산소 상태 반응뿐 아니라 섬유화 및 염증 반응과도 연관되어 있음을 밝혀내며, 만성 신장질환에서의 세포 기반 병태생리학적 기전을 탐구하고 있습니다. 또한, 생물학적 신호전달 분자(예: Resact)와 유전자 조절 메커니즘을 이용한 모델 생물 연구를 통해 분자생물학적 기전을 해부하고 있습니다.
Figures are computed from collected data and may differ slightly.
The Mediterranean turbot Psetta maxima consists of two main genetically distinct lineages (western Mediterranean and ‘eastern secluded Mediterranean’ basins) as investigated by mitochondrial DNA analysis. Within the latter lineage, most haplotypes from the Sea of Azov were endemic and more than half of them derived from a single ancestral haplotype shared among all the eastern Mediterranean areas. There was no relation between morphotype variation in bony tubercles and mitochondrial genealogy.
Erythropoietin (Epo) and its receptor (EpoR) are indispensable to erythropoiesis. Although roles besides angiogenesis, such as neuroprotection and heart development, have been reported for the Epo-EpoR system, the precise contribution of Epo-EpoR to these nonhematopoietic tissues requires clarification. Exploiting a GATA-1 minigene cassette with hematopoietic regulatory domains, we established 2 lines of transgene-rescued EpoR-null mutant mice expressing EpoR exclusively in the hematopoietic lin
In response to anemia, erythropoietin (Epo) gene transcription is markedly induced in the kidney and liver. To elucidate how Epo gene expression is regulated in vivo, we established transgenic mouse lines expressing green fluorescent protein (GFP) under the control of a 180-kb mouse Epo gene locus. GFP expression was induced by anemia or hypoxia specifically in peritubular interstitial cells of the kidney and hepatocytes surrounding the central vein. Surprisingly, renal Epo-producing cells had a
Over 10% of the global population suffers from kidney disease. However, only kidney replacement therapies, which burden medical expenses, are currently effective in treating kidney disease. Therefore, elucidating the complicated molecular pathology of kidney disease is an urgent priority for developing innovative therapeutics for kidney disease. Recent studies demonstrated that intertwined renal vasculature often causes ischemia-reperfusion injury (IRI), which generates oxidative stress, and tha
A peptide (resact) associated with the eggs of the sea urchin, Arbacia punctulata, which stimulates sperm respiration rates by 5-10-fold, was purified and its amino acid sequence was determined. The sequence was found to be Cys-Val-Thr-Gly-Ala-Pro-Gly-Cys-Val-Gly-Gly-Gly-Arg-Leu-NH2. The peptide was subsequently synthesized by solid phase methods, amidated at the carboxyl-terminal Leu, and shown to be identical to the isolated, native material. The peptide half-maximally stimulated A. punctulata
Erythropoietin (Epo) is an indispensable erythropoietic hormone primarily produced from renal Epo-producing cells (REPs). Epo production in REPs is tightly regulated in a hypoxia-inducible manner to maintain tissue oxygen homeostasis. Insufficient Epo production by REPs causes renal anemia and anemia associated with chronic disorders. Recent studies have broadened our understanding of REPs from prototypic hypoxia-responsive cells to dynamic fibrogenic cells. In chronic kidney disease, REPs are t
The interaction between stem cells and their supportive microenvironment is critical for their maintenance, function, and survival. Whereas hematopoietic stem cells (HSCs) are among the best characterized of tissue stem cells, their precise site of residence (referred to as the niche) in the adult bone marrow has not been precisely defined. In this study, we found that a Gata2 promoter directs activity in all HSCs. We show that HSCs can be isolated efficiently from bone marrow cells by following
Transcription factor GATA-1 is essential for the development of the erythroid lineage. To ascertain whether strict control of GATA-1 expression level is necessary for achieving proper erythropoiesis, we established transgenic mouse lines expressing green fluorescent protein (GFP) under the control of the GATA-1 gene hematopoietic regulatory domain. We examined the GATA-1 expression level by exploiting the transgenic mice and found 2 GFP-positive hematopoietic progenitor fractions in the bone mar
In order to search for compounds with higher activity than thiazolo [5, 4-b], imidazo-[4, 5-b] and triazolo [4, 5-b] [1, 8] naphthyridine derivatives against Ps. aeruginosa, we synthesized some heterocyclic condensed 1, 8-naphthyridine derivatives by using bifunctional 6, 7-disubstituted 1, 8-naphthyridine as a starting material. Thiadiazolo [5, 4-b] and oxazolo [5, 4-b] [1, 8] naphthyridine derivatives (3) and (5) were prepared by hydrolysis of the 6-amino-7-chloro-3-ester (1) with sodium hydro
Placental activation of the renin-angiotensin system (RAS) plays a key role in the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined the role of ROS in preeclampsia by genetically modifying the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular antioxidant responses;
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