@article{oai:twinkle.repo.nii.ac.jp:00018180,
 author = {NIINAMI, Chikako and HAYASHI, Naoaki},
 issue = {12},
 journal = {東京女子医科大学雑誌},
 month = {Dec},
 note = {肝線維化発症のメカニズムにおいて,肝の非実質細胞の一つであるhepatic stellate cell (HSC)が中心的役割を演ずることが知られている.そこで本研究ではHSCが肝の線維化に伴ってどのように変化するかを検討した.HSCは,類洞の傍らの肝細胞と内皮細胞の間に,静止状態もしくは活性状態(活性型)の二つの状態で存在する.活性化は慢性的に肝に炎症が起こることで生じることが知られているが,HSCが活性化されると,HSC自体が形態変化して樹枝状突起がのびた細胞へと変化する.この活性化された細胞の表面にはPDGFやTGF-βに対するレセプターが提示され,細胞分裂は活発になりコラーゲン産生が充進する.そこで本研究においてはラットを用いた二つの肝硬変モデル(胆汁鬱滞型モデルと肝炎型モデル)を作製し,線維化の各段階において活性型HSCマーカー(desmin, bFGF, α-SMA, PDGFR)と静止期HSCマーカー(GFAP)を用いて免疫染色を行い,定量化を行った.さらにヒトの肝硬変組織においてもHSCマーカーを用いた免疫染色を行った.実験モデルにおいては,肝硬変線維化の進展に伴い,小葉内ではdesminとPDGFRで染色される活性型HSCが著明に増加し,GFAPで染色される静止期HSCは減少した.fibreus septaeでは,desmin, α-SMA, PDGFR, bFGF陽性のHSCが増加していた.一方ヒトの肝硬変組織では,PBCおよびAIH症例ともに小葉内ではPDGFR陽性HSCが増加しておりラット肝硬変モデルの結果と一致した., Although there are severa known markers for hepatic stellate cells (HSC). few studies have used multiple markers in vivo to compare models of experimental cirrhosis and human cirrhosis. The number and phenotype of HSCs was examined using the markers desmin, α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-β (PDGFR-β), glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor (bFGF). Human cirrhosis was compared to two rat models of cirrhosis: bile duct-ligated (BDL) and carbon tetrachioride (CCl_4)-induced. Expression of antigens on HSCs in lobular areas and fibrous septae were visualized by immunohistochemical staining and quantified by image analysis. In both the BDL and CCl_4 models, there was a significant increase in desmin and PDGFR-β cells in the lobular areas that correlated with the disease progression. Lobular GFAP expression in sham controls was significantly greater than desmin expression, indicating a GFAP^+/desmin lobular HSC subset. During the development of cirrhosis, a significant down-regulation of lobular GFAP expression occurred. In human cirrhosis, there was significant upregulation of PDGFR-β expression in lobular areas and α-SMA expression in the portal tract, but no GFAP or bFGF expression. In conclusion, similar patterns of expression of multiple HSC markers were observed in biliary and hepatitic cirrhosis, both experimentally and in human. Cirrhosis is associated with an increased number of HSC with expansion of a desmin^+/GFAP^- population.},
 pages = {702--712},
 title = {Use of Multiple Markers for In Vivo Characterization and Quantitation of Hepatic Stellate Cells in Experimental and Human Liver Cirrhosis},
 volume = {70},
 year = {2000}
}