保健学専攻
- Master's Courses
修士課程 - Doctoral Courses
博士課程
Adult Health Nursing成人看護学
STAFF
Professor
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Imatani, AkiraProfessor. 今谷 晃 教授
CONTACT
TEL:+81-22-717-7929
E-MAIL:aimatani*med.tohoku.ac.jp
(「*」を「@」に変換してください)
OUTLINE
Aging and host immune response to Helicobacter pylori (H.pylori) infection cause the transdifferentiation from gastric oxyntic glands to gastric atrophy and intestinal metaplasia. The deviation from this process may lead to gastric cancer. Therefore, the major interest of our research is to clarify the molecular mechanisms of the differentiation and carcinogenesis from the gastric epithelial stem cell under chronic inflammation and aging. We focus on stem cell-related genes such as homeobox genes Sox2 and Cdx2 as well as a transmembrane receptor Notch1. In our vitro and vivo analyses revealed that the interaction of these genes expression induced gastric atrophy and intestinal metaplasia through NF-kB, Akt, and Wnt/beta-catenin intracellular signaling. Recently, we have also established gastric organoids from aged murine models and human well-differentiated gastric cancer tissues, and researched cellular senescence, stem cell aging, and carcinogenesis with age based on the microarray-related gene expression profiling.
胃癌は、我が国において診断・治療の確立とともに死亡率は減少しているものの、超高齢化社会を迎え、年齢別罹患率は依然、加齢とともに高くなっている。加齢やHelicobacter pylori (H.pylori)感染によって、胃上皮幹細胞の分化能低下によって生じる胃粘膜萎縮や分化変更である腸上皮化生は胃癌発症の原因と考えられている。そこで、H.pyloriに対する免疫応答、幹細胞の分化変更・老化に着目して胃発癌の分子生物学的機序について研究を進めている。H.pylori 長期感染マウスや自然免疫関連分子の遺伝子改変マウスなどを用いて、胃粘膜萎縮や腸上皮化生の進展には、NF-kB、Akt、Wnt/beta-catenin 細胞内シグナルを介した、ホメオボックス遺伝子Sox2やCdx2、さらに幹細胞維持に関わる膜受容体Notch1の相互作用が重要であることを明らかにしている。最近では、加齢マウスやヒト分化型早期胃癌より胃オルガノイドを樹立して、遺伝子発現プロファイルを作成し幹細胞老化が関わる胃発癌機序についても研究を展開している。
ARTICLE
Takeuchi A, et al. Suppressed cellular senescence mediated by T-box3 in aged gastric epithelial cells may contribute to aging-related carcinogenesis. Cancer Res Commun. 2(8):772-783, 2022
URL:https://pubmed.ncbi.nlm.nih.gov/36923312/
Takahashi K, et al. Sox2 induces tumorigenesis and angiogenesis of early-stage esophageal squamous cell carcinoma through secretion of Suprabasin. Carcinogenesis. 41(11): 1543-1552, 2020
URL:https://pubmed.ncbi.nlm.nih.gov/32055838/
Asano N, et al. Cdx2 expression and intestinal metaplasia induced by H. pylori infection of gastric cells is regulated by NOD1-mediated innate immune responses. Cancer Res. 76(5):1135-1145, 2016
URL:https://pubmed.ncbi.nlm.nih.gov/26759244/
Asonuma S et al, Helicobacter pylori induces gastric mucosal intestinal metaplasia through the inhibition of interleukin-4-mediated HMG box protein Sox2 expression. Am J Physiol Gastrointest Liver Physiol. 297(2): G312-322, 2009
URL:https://pubmed.ncbi.nlm.nih.gov/19520737/