Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis
Pancreatic stellate cells are activated by proinflammatory cytokines: implications for pancreatic fibrogenesis
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DOI：
10.1136/gut.44.4.534
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发表时间：
1999-04-01
期刊：
影响因子：
24.5
通讯作者：
Wilson, JS
中科院分区：
文献类型：
--
作者：
Apte, MV;Haber, PS;Wilson, JS
背景-胰腺纤维化的发病机制尚不清楚。在肝脏中，星状细胞在被细胞因子和氧化应激等促纤维化介质激活时，通过合成更多的胶原蛋白和其他细胞外基质 (ECM) 蛋白，在纤维发生中发挥重要作用。目的-确定培养的大鼠胰腺星状细胞是否产生胶原蛋白和其他 ECM 蛋白，并表现出激活迹象：当暴露于细胞因子血小板时 方法-使用特异性多克隆抗体对培养的胰腺星状细胞进行 ECM 蛋白前胶原 III、胶原 I、层粘连蛋白和纤连蛋白的免疫染色。对于细胞因子研究，将一式三份的细胞孔与浓度不断增加的 PDGF 或 TGF-β 一起孵育。结果：培养的胰腺星状细胞对所有测试的 ECM 蛋白均呈强阳性染色。用 1、5 和 10 ng/ml PDGF 孵育细胞，导致细胞计数以及 H-3-胸苷掺入 DNA 中显着密切相关的增加。暴露于 0.25、0.5 和 1 ng/ml TGF-β 的星形细胞显示出 α 平滑肌肌动蛋白表达的剂量依赖性增加和胶原蛋白合成的增加；此外，TGF-β增加星状细胞上PDGF受体的表达。结论-胰腺星状细胞产生胶原和其他细胞外基质蛋白，并通过增加增殖和增加胶原合成来响应细胞因子PDGF和TGF-β。这些结果表明星状细胞在胰腺纤维发生中发挥重要作用。
Background-The pathogenesis of pancreatic fibrosis is unknown. In the liver stellate cells play a major role in fibrogenesis by synthesising increased amounts of collagen and other extracellular matrix (ECM) proteins when activated by profibrogenic mediators such as cytokines and oxidant stress.Aims-To determine whether cultured rat pancreatic stellate cells produce collagen and other ECM proteins, and exhibit signs of activation:when exposed to the cytokines platelet derived growth factor (PDGF) or transforming growth factor beta (TGF-beta).Methods-Cultured pancreatic stellate cells were immunostained for the ECM proteins procollagen III, collagen I, laminin, and fibronectin using specific polyclonal antibodies. For cytokine studies, triplicate wells of cells were incubated with increasing concentrations of PDGF or TGF-beta.Results-Cultured pancreatic stellate cells stained strongly positive for all ECM proteins tested. Incubation of cells with I, 5, and 10 ng/ml PDGF led to a significant close related increase in cell counts as well as in the incorporation of H-3-thymidine into DNA, Stellate cells exposed to 0.25, 0.5, and 1 ng/ml TGF-beta showed a dose dependent increase in alpha smooth-muscle actin expression and increased collagen synthesis; In addition, TGF-beta increased the expression of PDGF receptors on stellate cells.Conclusions-Pancreatic stellate cells produce collagen and other extracellular matrix proteins, and respond to the cytokines PDGF and TGF-beta by increased proliferation and increased collagen synthesis. These results suggest an important role for stellate cells in pancreatic fibrogenesis.