| Co-Investigator(Kenkyū-buntansha) |
KUMAGAI Naoki Yamaguchi University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (20234510)
SEKI Keisuke Yamaguchi University, Faculty of Medicine, Associate Professor, 医学部, 客員助教授 (50318820)
FUKUDA Ken Yamaguchi University, Hospital, Assistant Professor, 医学部附属病院, 講師 (70335751)
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| Research Abstract |
1)Regulation of cellular proliferation, apoptosis, and intercellular communication by growth factors and cytokines has been investigated in cultured human corneal epithelial cells and keratocytes. In epithelial cells, HGF, insulin, IGF-1,IGF-2, and EGF each stimulated cell proliferation, inhibited the induction of apoptosis by sodium nitroprusside, and elicited the activation of Akt, whereas TGF-β1 and TGF-β2 inhibited cell proliferation but had no effect on apoptosis or Akt activity. In keratocytes, PDGF, insulin, IGF-1,IGF-2, and EGF each stimulated cell proliferation, inhibited the induction of apoptosis, and elicited the activation of Akt, whereas basic FGF,KGF,NGF, and HGF stimulated cell proliferation but did not affect apoptosis or Akt activity. The inflammatory cytokine TNF-α and the Th2 cytokines IL-4 and IL-13 down-regulated epithelial barrier function. TNF-α also inhibited intercellular communication by gap junctions in keratocytes.
2)We showed that the activity of Rho was up
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-regulated in corneal epithelia cells cultured on fibronectin and that Rac activity was increased in these cells by culture on laminin.
3)The transcription factor NF-κB was shown to be required for IL-1-induced degradation of collagen by keratocytes. Dexamethasone and triptolide each inhibited this effect of IL-1.
4)The contractility of keratocytes was examined by culture of the cells in a collagen gel in the presence of various other extracellular matrix proteins. The addition of fibronectin to collagen gels containing keratocytes induced marked gel contraction in a time- and concentration-dependent manner. Fibronectin also induced cell spreading and the formation of actin stress fibers in the gel-embedded keratocytes.
5)We investigated the effects of oxygen concentration on cellular functions. Hyperoxia stimulated corneal epithelial wound healing, whereas hypoxia inhibited ZO-1 expression and disrupted the barrier function of corneal epithelial cells. Hyperoxia also inhibited the proliferation of epithelial cells, whereas both hypoxia and hyperoxia inhibited keratocyte proliferation. Less
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