ACTIVATION-DEPENDENT CONTRACTILITY OF RAT HEPATIC LIPOCYTES IN CULTURE AND IN-VIVO
ACTIVATION-DEPENDENT CONTRACTILITY OF RAT HEPATIC LIPOCYTES IN CULTURE AND IN-VIVO
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DOI：
10.1172/jci116769
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发表时间：
1993-10-01
影响因子：
15.9
通讯作者：
FRIEDMAN, SL
中科院分区：
文献类型：
--
作者：
ROCKEY, DC;HOUSSET, CN;FRIEDMAN, SL
肝脂细胞是窦周细胞，被认为类似于组织周细胞。一种据称具有血管调节特性的细胞类型。然而，我们和其他人最近已经证明，脂肪细胞获得平滑肌细胞或肌成纤维细胞的标志物，只有在肝损伤后，通过一个过程称为"激活"。在这项研究中，我们记录了胶原晶格上的脂肪细胞收缩性，并研究了激活在这一过程中的重要性。在培养中，脂肪细胞仅在伸展和活化后才变得收缩，与平滑肌α肌动蛋白（活化的标志物）的表达一致（1990. Virchows Arch. B细胞病理学59：349）。在培养5天后，脂肪细胞诱导胶原晶格的快速和持续收缩（在脱离后24小时达到其原始大小的43.7 +/-2.3%）。含有肝细胞的晶格没有收缩。扫描电子显微镜显示脂肪细胞膜和胶原纤维的密切联系。收缩期间细胞体积的减少也很突出。脂肪细胞的晶格收缩与细胞数量成正比。血清是脂肪细胞收缩的有效刺激物，内皮素1型、2型和3型也是如此;血清和内皮素1的作用是相加的。凝血酶、血管紧张素II、5-羟色胺和细胞因子PDGF和TGF β均不诱导收缩。细胞松弛素B处理导致浓度依赖性的收缩抑制。作为培养结果的体内相关性的测试，从纤维化动物中分离脂肪细胞，并在粘附后立即进行检查。而来自正常肝脏的脂肪细胞最初是紧凑的，平滑肌α肌动蛋白阴性和非收缩性的，来自由于CCl4肝损伤的动物的细胞显示活化的外观，表达平滑肌α肌动蛋白，并且在粘附后立即收缩。此外，IFN-γ，一种阻断脂肪细胞活化的试剂（1992.肝病学。16：776），抑制脂肪细胞收缩。数据文档正常（即，静止的）脂肪细胞不收缩，但这种激活与收缩性的发展有关。这些发现表明，脂肪细胞在器官收缩或血管调节中的作用可能仅限于受损的肝脏，而不是正常的肝脏。
Hepatic lipocytes are perisinusoidal cells that have been thought to be analogous to tissue pericytes. a cell type with purported vasoregulatory properties. However, we and others have recently demonstrated that lipocytes acquire markers of smooth muscle cells or myofibroblasts only after liver injury, via a process termed ''activation.'' In this study, we document lipocyte contractility on collagen lattices and examine the importance of activation in this process. In culture, lipocytes became contractile only after spreading and activating, coincident with expression of smooth muscle alpha actin, a marker of activation (1990. Virchows Arch. B Cell Pathol. 59:349). After 5 d in culture, lipocytes induced rapid and sustained contraction of collagen lattices (to 43.7+/-2.3% of their original size 24 h after detachment). There was no contraction of lattices containing hepatocytes. Scanning electron microscopy demonstrated intimate associations of lipocyte cell membranes and collagen fibrils. Reduction in cell volume during contraction was also prominent. Lattice contraction by lipocytes was proportional to cell number. Serum was a potent stimulator of lipocyte contraction, as were endothelin types 1, 2, and 3; the effect of serum and endothelin 1 were additive. Neither thrombin, angiotensin-II, serotonin, nor the cytokines PDGF and TGFbeta induced contraction. Cytochalasin B treatment resulted in concentration-dependent inhibition of contraction.As a test of the in vivo relevance of the culture findings, lipocytes were isolated from fibrotic animals and examined immediately after adherence. Whereas lipocytes from normal liver were initially compact, smooth muscle alpha actin negative and noncontractile, cells from animals with hepatic injury due to CCl4 displayed an activated appearance, expressed smooth muscle alpha actin, and were contractile immediately after adherence. Additionally, IFN-gamma, an agent which blocks lipocyte activation (1992. Hepatology. 16:776), inhibited lipocyte contraction. The data document that normal (i.e., quiescent) lipocytes are not contractile, but that activation is associated with the development of contractility. These findings suggest that a role for lipocytes in organ contraction or vasoregulation may be confined to injured, not normal liver.