Angiotensin II enhances EGF receptor expression levels via ROS formation in HaCaT cells
Angiotensin II enhances EGF receptor expression levels via ROS formation in HaCaT cells
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DOI：
10.1016/j.jdermsci.2008.03.004
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发表时间：
2008-09-01
影响因子：
4.6
通讯作者：
Kubota, Yasuo
中科院分区：
文献类型：
--
作者：
Nakai, Kozo;Yoneda, Kozo;Kubota, Yasuo
背景：最近的研究表明，血管紧张素II(Ang II)在皮肤创面加热中具有新的作用，可能与活性氧有关。由于Ang II通过激活一些非吞噬细胞中的NADPH氧化酶而增加超氧化物的产生，我们推测NADPH激活产生的超氧化物可能参与角质形成细胞中表皮生长因子受体(EGFR)的调节。目的：研究Ang II是否能产生超氧化物并增强HaCaT细胞中EGFR的表达水平。结果：血管紧张素转换酶II(1-100 mU M)可促进超氧化物歧化。Ang II(1-100 mU M)可剂量依赖性地促进HaCaT细胞的增殖。肝素结合的表皮生长因子在5-10分钟内激活EGFR。虽然Ang II不能激活EGFR，但经Ang II(1mU M)处理6h后，HaCaT细胞的EGFR蛋白表达水平增加，NADPH氧化酶抑制剂apocynin可降低EGFR的表达水平。外源超氧化物生成系统黄嘌呤/黄嘌呤氧化酶系统促进了EGFR蛋白的表达。尽管血管紧张素Ⅱ不影响一氧化氮(NO)的产生，但一氧化氮合酶抑制剂N-奥米伽-硝基-L-精氨酸甲酯抑制血管紧张素Ⅱ诱导的表皮生长因子受体的表达。结论：Ang II通过调控HaCaT细胞产生超氧化物歧化产物促进细胞增殖和EGFR的表达，提示Ang II可能通过调节超氧化物和NO的生成来调节表皮的增殖、分化和肿瘤的发生。(C)2008年日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
Background: Recent work has shown a novel function of angiotensin II (Ang II) in skin wound heating in which reactive oxygen species might be involved. As Ang II is known to increase superoxide production by activating NADPH oxidase in some non-phagocytic cells, we hypothesized that the produced superoxide by NADPH activation could contribute to the regulation of epidermal growth factor receptor (EGFR) in keratinocytes.Objective: We examined whether Ang II could generate superoxide and enhance EGFR expression levels in HaCaT cells.Methods: Superoxide formation was assessed by using hydroethidine. EGFR expression levels were examined by Western blotting.Results: Ang II (1-100 mu M) increased the superoxide formation. Ang II (1-100 mu M) resulted in a dose-dependent increase in cell proliferation in HaCaT cells. Heparin-binding epidermal growth factor activated the EGFR at 5-10 min. Although Ang II did not activate the EGFR, the expression levels of EGFR protein were increased in HaCaT cells treated with Ang II (1 mu M) at 6 h. Apocynin, a NADPH oxidase inhibitor, decreased the expression levels of EGFR. Xanthine/xanthine oxidase system, an exogenous superoxide generating system, enhanced the EGFR protein expression. Although Ang II did not affect the nitric oxide (NO) production, a NO synthase inhibitor N-omega-nitro-L-arginine methyl ester suppressed the Ang II-induced EGFR expression levels in HaCaT cells. Thus, constitutive NO is required for the Ang II-induced EGFR expression in HaCaT cells.Conclusion: These results suggest that Ang II enhances the cell proliferation and EGFR expression via superoxide production under the regulation of NO in HaCaT cells, implying that Ang II may regulate the proliferation, differentiation and tumorigenesis of the epidermis by harmonizing the Superoxide and NO production. (c) 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.