Heterogeneity of liver cells expressing procollagen types I and IV in vivo
Heterogeneity of liver cells expressing procollagen types I and IV in vivo
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DOI：
10.1007/s004180050126
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发表时间：
1997-05-01
影响因子：
2.3
通讯作者：
Schuppan, D
中科院分区：
文献类型：
--
作者：
Herbst, H;Frey, A;Schuppan, D
纤维化肝的细胞外基质主要由间充质细胞产生，其体内表型不明确。我们报道了用[S-35]标记的α 1(I)和α 1（IV）前胶原RNA探针联合免疫组织学和原位杂交的应用。在ccl4处理的大鼠中，所有α 1(I)前胶原生成细胞均呈波形蛋白阳性，而细胞角蛋白阴性；90%以上表达大鼠肝星状细胞标记物desmin。α 1(I)原胶原表达，desmin阴性细胞局限于门静脉和血管周围基质。同样，在所有情况下，α 1(I)前胶原基因转录物在人肝脏中都与vimentin共定位。在纤维化标本中，超过70%的细胞表达α -肌动蛋白。针对上皮细胞、内皮细胞和库普弗细胞、粒细胞和淋巴细胞的抗体与α 1(I)前胶原rna表达细胞不发生反应。α 1(I)原胶原表达细胞的定位、形态和免疫表型表明，星状细胞和门脉/血管成纤维细胞是肝间质胶原的来源，而不是上皮细胞。然而，大多数表达α 1（IV）的人肝细胞被鉴定为内皮细胞，其余的细胞是（肌）成纤维细胞和胆管上皮细胞，而不是肝细胞。这表明基底膜两侧合成了IV型前胶原，表明内皮细胞积极参与了窦状动脉毛细血管化过程。
The extracellular matrix of fibrotic liver is predominantly produced by mesenchymal cells, the in vivo phenotype of which is poorly defined. We report on the application of combined immunohistology and in situ hybridization with [S-35]-labeled alpha 1(I) and alpha 1(IV) procollagen RNA probes. In CCl4-treated rats, all alpha 1(I) procollagen-producing cells were vimentin positive but cytokeratin negative; over 90% expressed desmin, a marker of rat liver stellate cells. alpha 1(I) Procollagen-expressing, desmin-negative cells were confined to portal tract and perivascular stroma. Similarly, alpha 1(I) procollagen gene transcripts were, in all instances, colocalized with vimentin in human liver. In fibrotic specimens, over 70% of these cells expressed alpha-actin. Antibodies against epithelial, endothelial, and Kupffer cells, granulocytes, and lymphocytes did not react with alpha 1(I) procollagen RNA-expressing cells. Localization, morphology, and immunophenotype of alpha 1(I) procollagen-expressing cells indicated stellate cells and portal/vascular fibroblasts, but not epithelial cells, to be sources of hepatic interstitial collagen. However, most alpha 1(IV)-expressing human Liver cells were identified as endothelial cells, the remaining cells were (myo-)fibroblastic and bile duct epithelial cells, but not hepatocytes. This indicates synthesis of procollagen type IV from both sides of the basement membrane and suggests an active participation of endothelial cells in the process of sinusoidal capillarization.