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1 KISEP Information Korean J Otolaryngol 2006;49: 후각신경상피세포의분화와재생 김정훈 Differentiation and Regeneration of Olfactory Neuroepithelial Cells Jeong-Whun Kim, MD Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University, Bundang Hospital, Seongnam, Korea - 248

Neuronal stem cells red give rise to transit amplifying progenitors that express Mash1 blue, followed by immediate neuronal precursors INPspurple, which express Neurogenin1 Ngn1.

2 김정훈 Stem cell Mash1 + Progenitor INP Ngn1 + ORN NCAM + NC OE GBC HBC LP OEC Fig. 1. Scheme of the neuronal differentiation pathway and histological arrangement of cells in mature olfactory neuroepithelium. Neuronal stem cells red give rise to transit amplifying progenitors that express Mash1 blue, followed by immediate neuronal precursors INPspurple, which express Neurogenin1 Ngn1. The INP divides and daughter cells differentiate into ORNs green, which are distinguished by NCAM expression. SUSSustentacular cells, adjacent to the nasal cavity, ORN olfactory receptor neuron layers, GBCglobose basal cell layer, containing stem cells and committed neuronal progenitors Mash1+progenitors and Ngn1+INPsHBChorizontal basal cell layer, LPlamina propria, OEColfactory enshe-athing cells, ONolfactory nerve axons of ORNsAdapted from Exp Cell Res ON SUS ORN Stem/ Progenitor Cells BL

3 후각신경상피의재생 Table 1. Identification of cell types in the olfactory neuroepithelium Antibody/Antigen Target Dilution Used GBC-1 rat OE GBCs 1300 Schwob Source GBC-2 rat OE GBCs 130 Schwob MASH1 GBCs bbs-1 carbohydrate HBCs, some glands 150 Vector Cytokeratin 5, 14 HBCs 150 Boehringer mannheim Nestin, monclonal Embryonic stem cells 150 Chemicon Olfactory marker protein OMP Mature neurons 15,000 Margolis et al. ß-tubulin isotype Neurons/progenitor 1100 Sigma NCAM, Monoclonal Neuronsall stages 150 Chemicon Vimentin Neurons 1100 Boehringer mannheim FGF2 Mature neurons; sustentacular cells 1100 UBI NGF receptor P75 Neurons and glia 150 Sigma GFAP, polyclonal Ensheathment progenitor 15 INCSTAR GAP-43 Immature neurons 130 TuJ-1 Neurotubulin Immature neurons 1100 Carter SUS-4 rat OE Sustentacular cells 110 Schwob Cytokeratin 18 Sustentacular cells 150 Serotec GLA-13 Bowman s glands and ducts 110 GFAP, monoclonal Ensheathment progenitorastrocytesolfactory glia 140 Boehringer mannheim A2B5, monoclonal Glia/some neurons 1100 Boehringer mannheim PCNA Mitotically active cells 15,000 Sigma BrdU Mitotically active cells 150 Becton-dickinson Korean J Otolaryngol 2006;49:248-56

PCNApositive cells could be rarely found and localized mainly

SO 2 exposure B, and this finding was also observed 7 days C,

The PCNA-positive cells were found mainly in the superficial

4 김정훈 A B C E D F Fig. 2. Expression of proliferating cell nuclear antigen PCNA after exposure to SO 2. The mice were exposed to 40 ppm SO 2 for 2 hours. PCNApositive cells could be rarely found and localized mainly in the basal cell layer of the olfactory neuroepithelium of control mice A. The immunoreactivity of PCNA markedly increased 5 days after SO 2 exposure B, and this finding was also observed 7 days C, 10 days D, and 14 days E after SO 2 exposure. The PCNA-positive cells were found mainly in the superficial layer 5 days after SO 2 exposure. The number of PCNA-positive cells increased in the basal cell layer between 7 and 14 days after SO 2 exposure. The number of PCNApositive cells decreased 21 days F after SO 2 exposure

5 후각신경상피의재생 Korean J Otolaryngol 2006;49:248-56

6 김정훈 in vitro - HBC GBC mpp TGF- OSN m IGF-1 GBC ta FGF2 OSN i BMP 2, 4, 7 GBC inp TGF-s PDGF Fig. 3. Growth factor regulation on the processes of cellular renewal in the olfactory epithelium apparently depends on similar factors playing similar roles as in other systems. The balance between fibroblast growth factor-2 FGF-2 and BMP signals seems to be critical for advancing or retarding neurogenesis. Transforming growth factors- TGF- stimulate neuronal differentiation in cell lines derived from GBCs. Lines ending in circles designate a stimulatory effect; lines ending in a perpendicular line indicate inhibition. IGF-1insulin-like growth factor-1, PDGF platelet-derived growth factor, GBCglobose basal cells, mppmulti-potent precursors, tatransit amplifying, inp immediate neuronal precursors, OSN mmature olfactory sensory neurons, OSN iimmature olfactory sensory neuron, HBC horizontal basal cells, SUSsustentacular cells Adapted from Anat Rec 2002;269: SUS 253

7 후각신경상피의재생 in vitro 254 Korean J Otolaryngol 2006;49:248-56

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Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract