Interleukin (IL)-13, Prostaglandin E2 (PGE2), and Prostacyclin 2 (PGI2) Activate Hepatic Stellate Cells via Protein kinase C (PKC) Pathway in Hepatic Fibrosis.
Interleukin (IL)-13, Prostaglandin E2 (PGE2), and Prostacyclin 2 (PGI2) Activate Hepatic Stellate Cells via Protein kinase C (PKC) Pathway in Hepatic Fibrosis.
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DOI：
10.12659/msm.906442
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发表时间：
2018-04-10
期刊：
影响因子：
--
通讯作者：
Niu H
中科院分区：
文献类型：
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作者：
Sui G;Cheng G;Yuan J;Hou X;Kong X;Niu H
蛋白激酶 C (PKC)、白细胞介素 (IL)-13、前列腺素 E2 (PGE2) 和前列环素 2 (PGI2) 都在肺纤维化中发挥重要作用。然而，它们在肝星状细胞（HSC）介导的肝纤维化中的功能仍不清楚，已被证明与转化生长因子-β（TGF-β）和血小板源性生长因子（PDGF）有关。所有实验均基于LX-2肝星状细胞。通过 ELISA、RT-PCR 和 Western blotting 分别评估经 IL-13、PGE2 和 PGI2 处理的人 HSC 中 TGF-β1 和 PDGF 的表达。同时，采用桥法和CCK8法检测细胞增殖和活性，采用PKC活性测定法检测PKC的活性，并采用PKC激动剂和拮抗剂验证之前得到的结果。我们发现IL-13、PGE2和PGI2显着增强人HSC中TGF-β1和PDGF的表达，这也明显改善了HSC的增殖和细胞活性。此外，IL-13、PGE2 和 PGI2 治疗后 PKC 活性显着增加。我们还发现，PKC 激动剂佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA) 显着增强 TGF-β1 和 PDGF 的表达以及 HSC 的增殖和细胞活性，但被 PKC 拮抗剂 calphostin C 抑制。我们发现 IL-13、PGE2 和 PGI2 通过激活 PKC 刺激 HSC 增殖和分泌 TGF-β1 和 PDGF，这预测了它们的潜力在肝纤维化中的作用。
Protein kinase C (PKC), interleukin (IL)-13, prostaglandin E2 (PGE2), and prostacyclin 2 (PGI2) can all play crucial roles in pulmonary fibrosis. However, their functions remain unclear in hepatic fibrosis mediated by hepatic stellate cells (HSCs), which has been demonstrated to be related to transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF). All the experiments were based on LX-2 Hepatic stellate cells. The expression of TGF-β1 and PDGF were assessed by ELISA, RT-PCR, and Western blotting in human HSCs treated by IL-13, PGE2, and PGI2, respectively. At the same time, bridge assay and CCK8 assay were used to detect the cell proliferation and activity, PKC activity assay was used to test the activity of PKC, and PKC agonist and antagonist were used to verify the results obtained previously. We found that IL-13, PGE2, and PGI2 significantly enhanced the expression of TGF-β1 and PDGF in human HSCs, which also clearly improved the proliferation and cell activity of HSCs. Moreover, PKC activity was significantly increased following IL-13, PGE2, and PGI2 treatments. We also found that the expression of TGF-β1 and PDGF, as well as the proliferation and cell activity of HSCs, were significantly enhanced by the PKC agonist phorbol 12-myristate 13-acetate (PMA), but suppressed by the PKC antagonist calphostin C. We found that IL-13, PGE2, and PGI2 stimulated HSCs proliferation and secretion of TGF-β1 and PDGF by activating PKC, which predicted their potential roles in hepatic fibrosis.
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影响因子：
4.4
作者：
Liu X;Lu R;Xia Y;Sun J
通讯作者：
Sun J
影响因子：
25.7
作者：
ANNONI, G;WEINER, FR;ZERN, MA
通讯作者：
ZERN, MA
DOI：
10.1073/pnas.79.3.749
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
RICKLES, R;MARASHI, F;STEIN, G
通讯作者：
STEIN, G
炎症相关细胞因子的组合可促进肌肉干细胞的长期扩增。
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
13.5
作者：
FRIEDMAN, SL;ROCKEY, DC;YAMASAKI, G
通讯作者：
YAMASAKI, G