Transforming growth factor-β induces contraction of activated hepatic stellate cells
Transforming growth factor-β induces contraction of activated hepatic stellate cells
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DOI：
10.1016/j.jhep.2004.03.019
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发表时间：
2004-07-01
影响因子：
25.7
通讯作者：
Tuma, DJ
中科院分区：
文献类型：
--
作者：
Kharbanda, KK;Rogers, DD;Tuma, DJ
背景/目的：转化生长因子-β（TGF-β）是一种在肝损伤过程中大量产生的细胞因子。认识到突出的作用，肝星状细胞（HSC）和TGF-β发挥门静脉高压症和纤维化，分别，我们试图评估TGF-β对激活HSCs.Methods的收缩性的影响：自发永生化细胞系的HSC起源在这项研究中使用。细胞在三维胶原凝胶网格中生长，转移到60 mm培养皿中，并在37 ℃下暴露于无血清培养基中不同浓度的TGF-β 1长达120 h。使用Fluor S-MultiImager（Biorad）测量漂浮凝胶的面积，定量细胞平滑肌-α肌动蛋白（SMA）含量并进行PKC活化studies.Results：TGF-β 1诱导晶格面积的时间和剂量依赖性减少，最多为对照的40%（P < 0.05），这反映了活化的HSC的收缩。这种诱导的收缩与这些细胞中SMA含量（3倍，P < 0.05）和PKC活化（5倍，P < 0.05）的增加相关。此外，预孵育与PKC-β特异性抑制剂完全废除了TGF-β诱导的contractions.Conclusions：TGF-β诱导收缩激活的HSC通过增加SMA含量和PKC-β介导的途径。(C)2004年欧洲肝脏研究协会。Elsevier B. V.出版，保留所有权利。
Background/Aims: Transforming growth factor-beta (TGF-beta) is a cytokine produced in abundance during liver injury. Recognizing the prominent roles that hepatic stellate cells (HSCs) and TGF-beta play in portal hypertension and fibrogenesis, respectively, we sought to evaluate the effect of TGF-beta on the contractility of activated HSCs.Methods: Spontaneous immortalized cell lines of HSC origin were used in this study. Cells were grown in three-dimensional collagen gel lattice, transferred to 60 mm dishes and exposed to varying concentrations of TGF-beta1 in serum-free medium at 37 degreesC for up to 120 h. The area of the floating gels was measured using a Fluor S-MultiImager (Biorad), the cellular smooth muscle-alpha actin (SMA) content quantified and PKC activation studies conducted.Results: TGF-beta1 induced a time- and dose-dependent decrease in lattice area up to 40% of control (P < 0.05) that reflects the contraction of activated HSCs. This induced contraction was associated with increases in SMA content (3-fold, P < 0.05) and PKC activation (5-fold, P < 0.05) in these cells. Furthermore, pre-incubating with a PKC-epsilon-specific inhibitor completely abrogated the TGF-beta-induced contraction.Conclusions: TGF-beta induces contraction of activated HSCs via an increase in SMA content and a PKC-epsilon-mediated pathway. (C) 2004 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.