We study Institute for Molecular Science of Medicine, 1st Department about extracellular matrix element particularly Structure and Function of proteoglycan and glycosaminoglycan, participation in condition of a patient consistently. This Laboratory accumulates results of research to pull the world in the field concerned.
Institute for Molecular Science of Medicine is independent, and it performs postgraduate education. We teach the basics of experiment technology, the acquisition of basic knowledge, making of study plan, interpretation of result, writing of article and aim at first rank English sentence magazine publication, graduation of graduate student. We are in charge of the field of carbohydrate chain of natural science, Biochemistry, Molecular Patho-biochemistry and extracellular matrix for School of Medicine student.
Activity, Research Contents
Keyword of study that Institute for Molecular Science of Medicine deals with is extracellular matrix, proteoglycan, glycosaminoglycan.
Multicellular organism has structure called extracellular matrix outside cell and occupies farther than cell big volume. We control increase, differentiation of cell without extracellular matrix being comprised of molecules group such as hyaluronic acid, proteoglycan making up for collagen fiber, fibrous ingredients such as elastic fiber and the gap, and supporting cell, and giving nourishment, and it being for retaining biologically active molecule, and forming concentration gradient. We focus on representative molecules of particularly huge chondroitin sulfate/dermatan sulfate proteoglycan, agricultural perception and bashikan, and we study about Structure and Function of extracellular matrix.
Proteoglycan is defined as molecular group which carbohydrate chain called more than one glycosaminoglycan chains covalently bound by protein called core protein. There is proteoglycan on not only extracellular matrix but also the cell membrane top and we regulate signal transmission to cell as co-receptor and control, and carbohydrate chain called glycosaminoglycan mainly takes this function. We study about shown specific function by chondroitin sulfate, construction mechanism and carbohydrate chain structure of minute carbohydrate chain of heparan sulfate.
It is place of permeation of inflammation and cancer, and extracellular matrix is connected directly with various pathologic formation and progress. We cooperate with clinical system Seminars such as Orthopedic Surgery, plastic surgery, Dermatology about cartilage which is rich in extracellular matrix, function of Organization such as skin and participation in condition of a patient positively and promote collaborative investigation.
Concrete study themes are as follows.
- Participation in representative giant proteoglycan of extracellular matrix, invivo function of bashikan and pathologic formation, progress
- Central huge proteoglycan playing its part of cartilage function, function and metabolism of agricultural perception
- Elucidation of biosynthesis mechanism of chondroitin sulfate
- Bioengineering of chondroitin sulfate
- Search of specific function based on carbohydrate chain structure of chondroitin sulfate
- Participation in elucidation of sulfation mechanism of heparan sulfate, elucidation of fine structure of the carbohydrate chain and specific function and pathologic formation, progress
|Full name||Job title||Specialized field|
|WATANABE Hideto||Professor||Molecular pathology|
|NAGAI Naoko||Assistant Professor||Cell biology, molecular biology|
|HATANO Sonoko||Assistant Professor||Molecular biology, dietetics|
|TSUCHIMOTO Jun||Assistant Professor||Molecular biology, developmental biology|
|Tatsumasa Shioiri||Assistant||Carbohydrate chain Biochemistry|
|Full name||Research Theme|
Study career and study contents of Professor Watanabe
I Watanabe was engaged in extracellular matrix, study of connective tissue for 25 years or more. It was Pathology Speciality Course in Graduate School, but, in Medical Res. Inst., Tokyo Medical and Dental Univ. abnormal metabolism Departments (Professor Hiroshi Nagai) of temporary study at a university within the country, we analyzed metabolism of collagen and the refinement and property of extracellular matrix degrading enzyme and analyzed agricultural perception and gene cloning, transcription control of link protein, gene defect mouse which formed proteoglycan meeting body which was cartilaginous major components in the United States Kunitachi dentistry chin face Institute, the National Institutes of Health (National Institute of Dental and Craniofacial Research, National Institutes of Health) of studying abroad ahead.
We are continuing studying about structure, function, metabolism of agricultural perception sequentially now. Agricultural perception gives glass-like form and elasticity to cartilage having strong earth-water preservation action. It is cartilage matrix molecules becoming preventive key in the cartilage destructivity diseases such as osteoarthritis and expects that result of this study is connected for the condition of a patient progress check of these diseases.
Five gene families are identified about agricultural perception in total. Of these, in bashikan emerging in mesenchyma system Organization widely, it is thought with prototype of the family. The molecules were found to participate in outbreak, inflammation and cancer invasion of heart and hair follicle. We analyze invivo function of bashikan using various kinds of gene modification mice.
This century begins, and chondroitin sulfate synthase is found in sequence, and six kinds of enzymes are identified now. We mainly aim at elucidation of each invivo function of these enzymes through gene modified murine analysis.
Study introduction (Nagai)
Heparan sulfate is combined with protein called proteoglycan and exists outside cell surface and cell. It is molecules which a lot of bases sulfate unite according to the name. Heparan sulfate has protein about various kinds of growth factors and neovascularisation promoting increase, various protein such as protein which participates to form of body and property to interact of cell. Therefore, heparan sulfate works to modify various life phenomena such as cell proliferation, cell differentiation, cell migration, organogenesis, uptake of molecules in cell. We are pushing forward the following study about this heparan sulfate now.
- (1) where I found that heparan sulfate participated in the onset of metabolic syndrome using knockout mouse of enzyme which added basis sulfate to heparan sulfate. We are checking whether heparan sulfate modifies function of what kind of protein, and you control murine metabolism now.
- Enzyme Hs6st2 adding basis sulfate to heparan sulfate has an N-terminal side to cytoplasm, and C-terminal side is once transmembrane protein in Goldi body. By identification of phosphorylated amino acid and identification of interacting protein, we use mass spectrometry device to check function of this cytoplasmic domain.
Study summary (Hatano)
Proteoglycan constituting extracellular matrix (ECM) is doing structure that carbohydrate chain called sulfation glycosaminoglycan (GAG) was added to to core protein. It is known by proteoglycan that we have a variety of functions for cell by controlling bioactive factor from the cellular outside. I study invivo function of chondroitin sulfate (CS) which is kind of bashikan and GAG which are one of the core proteins.
１．There is role that bashikan is combined with hyaluronic acid and contributes to stabilization of ECM. With bashikan variation mouse which reduced this combination, he dies of heart hypoplasia just after birth. In addition, the formation of skin gets worse and becomes weak skin (Hatano S. et al., Glycobiology, 2012, Hatano S. et al., Connective Tissue Research, 2018).
２．We manufactured mouse which deleted one of the synthase to clarify invivo function of CS. The CS carbohydrate chain head shortened with this murine cartilage, but did not influence the murine frame formation (Ogawa H, Hatano S et al., PLoS One, 2012). Because CS synthase is several kinds, and this forms aggregate, and it is thought that we make up for the work each other, we manufacture mouse which deleted plural connection enzymes and are pushing forward analysis now.
Extracellular matrix, proteoglycan, glycosaminoglycan, hyaluronic acid, chondroitin sulfate, heparan sulfate, collagen, gene modification mouse, Glycoscience
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