Researchers

Research Activities

Research Areas

• Life sciences, Tumor biology
• Life sciences, Cell biology
• Life sciences, Molecular biology
• Life sciences, Pharmacology
• Life sciences, Physiology
• Life sciences, Pathobiochemistry
• Life sciences, Experimental pathology

Research Interests

HGFによる組織再生, PTEN・p53による癌抑制, 慢性腎不全の診断・治療, COPD治療, ネフローゼ症候群の分子機構

Published Papers

1. Immunofluorescence Detection of Plasma Membranous PTEN in Cultured Cells
   Takashi Kato
   Journal of Histochemistry & Cytochemistry  , 002215542210825-002215542210825, 24, Feb. 2022 
2. Generating a new mouse model for nuclear PTEN deficiency by a single K13R mutation.
   Takashi Kato; Atsushi Igarashi; Hiromi Sesaki; Miho Iijima
   Genes to cells : devoted to molecular & cellular mechanisms  26  (12)  , 1014-1022, Dec. 2021 
3. Nuclear PTEN deficiency and heterozygous PTEN loss have distinct impacts on brain and lymph node size
   Atsushi Igarashi; Takashi Kato; Hiromi Sesaki; Miho Iijima
   Biochemical and Biophysical Research Communications  555  , 81-88, 21, May. 2021  , Refereed

MORE

MISC

1. Renal ADAM10 and 17: Their Physiological and Medical Meanings. , Takashi Kato; Man Hagiyama; Akihiko Ito , Frontiers in cell and developmental biology , 6 , 153 , 153 , 2018
   Summary:A disintegrin and metalloproteinases (ADAMs) are a Zn2+-dependent transmembrane and secreted metalloprotease superfamily, so-called "molecular scissors," and they consist of an N-terminal signal sequence, a prodomain, zinc-binding metalloprotease domain, disintegrin domain, cysteine-rich domain, transmembrane domain and cytoplasmic tail. ADAMs perform proteolytic processing of the ectodomains of diverse transmembrane molecules into bioactive mediators. This review summarizes on their most well-known members, ADAM10 and 17, focusing on the kidneys. ADAM10 is expressed in renal tubular cells and affects the expression of specific brush border genes, and its activation is involved in some renal diseases. ADAM17 is weakly expressed in normal kidneys, but its expression is markedly induced in the tubules, capillaries, glomeruli, and mesangium, and it is involved in interstitial fibrosis and tubular atrophy. So far, the various substrates have been identified in the kidneys. Shedding fragments become released ligands, such as Notch and EGFR ligands, and act as the chemoattractant factors including CXCL16. Their ectodomain shedding is closely correlated with pathological factors, which include inflammation, interstitial fibrosis, and renal injury. Also, the substrates of both ADAMs contain the molecules that play important roles at the plasma membrane, such as meaprin, E-cadherin, Klotho, and CADM1. By being released into urine, the shedding products could be useful for biomarkers of renal diseases, but ADAM10 and 17 per se are also notable as biomarkers. Furthermore, ADAM10 and/or 17 inhibitions based on various strategies such as small molecules, antibodies, and their recombinant prodomains are valuable, because they potentially protect renal tissues and promote renal regeneration. Although temporal and spatial regulations of inhibitors are problems to be solved, their inhibitors could be useful for renal diseases.
2. Biological roles of hepatocyte growth factor-Met signaling from genetically modified animals. , Takashi Kato , Biomedical reports , 7 , 6 , 495 , 503 , Dec. 2017
   Summary:Hepatocyte growth factor (HGF) is produced by stromal and mesenchymal cells, and it stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its cognate receptor, Met. The HGF-Met signaling pathway contributes in a paracrine manner to the development of epithelial organs, exerts regenerative effects on the epithelium, and promotes the regression of fibrosis in numerous organs. Additionally, the HGF-Met signaling pathway is correlated with the biology of cancer types, neurons and immunity. In vivo analyses using genetic modification have markedly increased the profound understanding of the HGF-Met system in basic biology and its clinical applications. HGF and Met knockout (KO) mice are embryonically lethal. Therefore, amino acids in multifunctional docking sites of Met have been exchanged with specific binding motifs for downstream adaptor molecules in order to investigate the signaling potential of the HGF-Met signaling pathway. Conditional Met KO mice were generated using Cre-loxP methodology and characterization of these mice indicated that the HGF-Met signaling pathway is essential in regeneration, protection, and homeostasis in various tissue types and cells. Furthermore, the results of studies using HGF-overexpressing mice have indicated the therapeutic potential of HGF for various types of disease and injury. In the present review, the phenotypes of Met gene-modified mice are summarized.
3. Targeting the hepatocyte growth factor/Met pathway in cancer. , Dinuka M De Silva; Arpita Roy; Takashi Kato; Fabiola Cecchi; Young H Lee; Kunio Matsumoto; Donald P Bottaro , Biochemical Society transactions , 45 , 4 , 855 , 870 , 15, Aug. 2017
   Summary:Hepatocyte growth factor (HGF)-induced activation of its cell surface receptor, the Met tyrosine kinase, drives mitogenesis, motogenesis and morphogenesis in a wide spectrum of target cell types and embryologic, developmental and homeostatic contexts. Typical paracrine HGF/Met signaling is regulated by HGF activation at target cell surfaces, HGF binding-induced receptor activation, internalization and degradation. Despite these controls, HGF/Met signaling contributes to oncogenesis, tumor angiogenesis and invasiveness, and tumor metastasis in many types of cancer, leading to the rapid growth of pathway-targeted anticancer drug development programs. We review here HGF and Met structure and function, basic properties of HGF/Met pathway antagonists now in clinical development, and recent clinical trial results. Presently, the main challenges facing the effective use of HGF/Met-targeted antagonists for cancer treatment include optimal patient selection, diagnostic and pharmacodynamic biomarker development, and the identification and testing of effective therapy combinations. The wealth of basic information, analytical reagents and model systems available regarding normal and oncogenic HGF/Met signaling will continue to be invaluable in meeting these challenges and moving expeditiously toward more effective cancer treatment.

Research Grants & Projects

1. Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Does nuclear PTEN have tumor suppressor functions independent of phosphatase activities? , Yasuda Women's University
2. 日本学術振興会, 科学研究費助成事業, 肺胞上皮・尿細管上皮細胞の変性病態モデルの作成とHGFによる治療の可能性 , 近畿大学
3. Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Establishment of model for lung adenocarcinoma in 3D and identification of promotional factor for stromal invasion , Kinki University