Restriction of Mast Cell Proliferation through Hyaluronan Synthesis by Co-cultured Fibroblasts

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  • Takano Hirotsugu
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Furuta Kazuyuki
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Yamashita Kazuhito
    Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
  • Sakanaka Mariko
    Department of Immunobiology, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University
  • Itano Naoki
    Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University
  • Gohda Eiichi
    Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
  • Nakayama Kazuhisa
    Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University
  • Kimata Koji
    Research Complex for the Medicine Frontiers, Aichi Medical University
  • Sugimoto Yukihiko
    Department of Pharmaceutical Biochemistry, Graduate School of Medicine and Pharmaceutical Sciences, Kumamoto University
  • Ichikawa Atsushi
    Institute for Biosciences, Mukogawa Women's University
  • Tanaka Satoshi
    Department of Immunobiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

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  • Highlighted Paper selected by Editor-in-Chief : Restriction of Mast Cell Proliferation through Hyaluronan Synthesis by Co-cultured Fibroblasts

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Abstract

Appropriate culture models for tissue mast cells are required to determine how they are involved in regulation of local immune responses. We previously established a culture model for cutaneous mast cells, in which bone marrow-derived immature mast cells were co-cultured with Swiss 3T3 fibroblasts in the presence of stem cell factor. In this study, we focused on the roles of hyaluronan, which is produced by the feeder fibroblasts and forms the extracellular matrix during the co-culture period. Hyaluronan synthesis was found to be mediated by hyaluronan synthase 2 (HAS2) expressed in Swiss 3T3 cells. A decreases in the amount of hyaluronan, which was achieved by retroviral expression of short hairpin RNA for Has2 or by addition of hyaluronidase, significantly enhanced the proliferation of the cultured mast cells without any obvious effects on their maturation. Although we previously demonstrated that CD44 is required for proliferation of cutaneous mast cells, the deficiency of hyaluronan did not affect the proliferation of the cultured mast cells that lack CD44. These findings suggest that the extracellular matrix containing hyaluronan may have a potential to restrict proliferation of cutaneous mast cells in a CD44-independent manner.

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