Morphological aspects of hepatic fibrosis and Ito cells (hepatic stellate cells), with special reference to their myofibroblastic transformation
Morphological aspects of hepatic fibrosis and Ito cells (hepatic stellate cells), with special reference to their myofibroblastic transformation
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肝纤维化和伊藤细胞（肝星状细胞）的形态学方面，特别是肌纤维母细胞转化
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
T. Saibara
中科院分区：
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作者：
H. Enzan;Y. Hayashi;E. Miyazaki;K. Naruse;R. Tao;N. Kuroda;H. Nakayama;H. Kiyoku;M. Hiroi;T. Saibara
Ito细胞通过最初的肌纤维母细胞转化在人类和实验动物的各种类型的肝纤维化中发挥主要作用。在肝细胞坏死后的肉芽组织中，转化的Ito细胞大且呈星形，通过α-平滑肌肌动蛋白（ASMA）的强免疫反应性和特征性电子显微镜检查结果（如发达的粗面内质网、大的高尔基复合体、细胞膜下有致密体的大量微丝束和不规则的胞质突起）容易识别。这些细胞与活化的枯否细胞、巨噬细胞、淋巴细胞和嗜中性粒细胞密切相关。在完全发育阶段，它们积极合成和分泌细胞外基质的成分，导致形成松散的年轻纤维组织。随着纤维化的进展，转化的Ito细胞变成梭形，并与致密的胶原纤维平行排列。他们失去了发达的粗面内质网和大型高尔基复合体，但有一个更显着的增加亚质膜微丝。这种类型的转化细胞，ASMA阳性，可能不参与细胞外基质成分的产生，但确实参与旧纤维化组织的收缩。另一方面，门静脉成纤维细胞在任何类型的纤维化中均未显示出显著变化。Ito细胞的肌纤维母细胞转化不仅见于纤维化，而且见于胎肝发育的晚期，此时窦周网状纤维比正常成人肝脏更丰富。这些发现表明，肌纤维母细胞转化的伊藤细胞，在纤维化中最重要的事件，是一个重演的正常发育过程。
Ito cells play a major role in various types of liver fibrosis in humans and experimental animals through initial myofibroblastic transformation. In granulation tissue following liver cell necrosis, the transformed Ito cells are large and star-shaped, and are easily identified by strong immunoreactivity for α-smooth muscle actin (ASMA), and characteristic electron-microscopic findings such as a well-developed rough endoplasmic reticulum, a large Golgi complex, bundles of numerous microfilaments with dense bodies beneath the cell membrane, and irregular cytoplasmic processes. These cells are closely associated with activated Kupffer cells, macrophages, lymphocytes, and neutrophils. In the fully developed stage they actively synthesize and secrete components of the extracellular matrix, resulting in the formation of the loose young fibrous tissue. With the progression of fibrosis, the transformed Ito cells become spindle-shaped and are arranged in parallel with dense collagen fibers. They lose both the well-developed rough endoplasmic reticulum and the large Golgi complex, but there is a more significant increase in subplasmalemmal microfilaments. This type of transformed cell, positive for ASMA, may not participate in the production of extracellular matrix components, but does participate in the contraction of old fibrotic tissue. On the other hand, portal fibroblasts show no significant changes in any type of fibrosis. The myofibroblastic transformation of Ito cells is seen not only in fibrosis, but also in the late stage of fetal liver development, when the perisinusoidal reticular fibers are more abundant than in normal adult livers. These findings suggest that the myofibroblastic transformation of Ito cells, the most important event in fibrosis, is a recapitulation of a normal developmental process.