TGF beta1 and PDGF AA override collagen type I inhibition of proliferation in human liver connective tissue cells.
TGF beta1 and PDGF AA override collagen type I inhibition of proliferation in human liver connective tissue cells.
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DOI：
10.1186/1471-230x-4-30
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发表时间：
2004-12-03
影响因子：
2.4
通讯作者：
Monteiro AN
中科院分区：
文献类型：
--
作者：
Geremias AT;Carvalho MA;Borojevic R;Monteiro AN
结缔组织群体的显著扩张和细胞外基质蛋白的异常沉积是肝组织慢性和急性损伤的标志。来源于纤维化肝脏的肝结缔组织细胞，也称为星状细胞，已被彻底表征，并在表型上对应于肌成纤维细胞。它们被认为来源于窦周隙中储存脂肪的Ito细胞，并且当被组织损伤激活时获得收缩表型。在过去的几年中，已经变得明显的是，几种肽生长因子如PDGF AA和TGF-β通过调节肌成纤维细胞增殖和胶原分泌而参与纤维化的发展。事实上，在慢性纤维化的发展过程中，伴随着胶原蛋白的沉积，一种已知的抑制因子，和持续的细胞增殖，提高了来自慢性肝纤维化患者的星状细胞不能响应正常生理控制的可能性。在这项研究中，我们解决了肝纤维化患者的细胞是否对正常对照的增殖反应。我们比较了来自肝纤维化患者的原代人肝结缔组织细胞（LCTC）和皮肤成纤维细胞（SF）在I型和IV型胶原、TGF-β、PDGF AA以及I型胶原和TGF-β或PDGF AA的组合存在下的细胞增殖。我们的研究结果表明，尽管显示正常的接触和胶原诱导的增殖抑制LCTC更有力地响应较低浓度的PDGF AA。此外，我们发现I型胶原与生长因子协同促进LCTC而不是SF的有丝分裂。生长因子和细胞外基质蛋白的协同作用可能是慢性肝纤维化发展的基础。
A marked expansion of the connective tissue population and an abnormal deposition of extracellular matrix proteins are hallmarks of chronic and acute injuries to liver tissue. Liver connective tissue cells, also called stellate cells, derived from fibrotic liver have been thoroughly characterized and correspond phenotypically to myofibroblasts. They are thought to derive from fat-storing Ito cells in the perisinusoidal space and acquire a contractile phenotype when activated by tissue injury. In the last few years it has become evident that several peptide growth factors such as PDGF AA and TGF-β are involved in the development of fibrosis by modulating myofibroblast proliferation and collagen secretion. The fact that during the development of chronic fibrosis there is concomitant deposition of collagen, a known inhibitory factor, and sustained cell proliferation, raises the possibility that stellate cells from chronic liver fibrosis patients fail to respond to normal physiologic controls. In this study we address whether cells from fibrotic liver patients respond to normal controls of proliferation. We compared cell proliferation of primary human liver connective tissue cells (LCTC) from patients with liver fibrosis and skin fibroblasts (SF) in the presence of collagens type I and IV; TGF-β, PDGF AA and combinations of collagen type I and TGF-β or PDGF AA. Our results indicate that despite displaying normal contact and collagen-induced inhibition of proliferation LCTC respond more vigorously to lower concentrations of PDGF AA. In addition, we show that collagen type I synergizes with growth factors to promote mitogenesis of LCTC but not SF. The synergistic interaction of growth factors and extracellular matrix proteins may underlie the development of chronic liver fibrosis.