Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis.
Anti-Inflammatory Action of Angiotensin 1-7 in Experimental Colitis.
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DOI：
10.1371/journal.pone.0150861
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Luqmani YA
中科院分区：
文献类型：
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作者：
Khajah MA;Fateel MM;Ananthalakshmi KV;Luqmani YA
有证据支持血管紧张素（Ang）1-7在降低炎症信号分子如MAPK、PKC和SRC的活性中的作用。在炎症性肠病（IBD）患者中观察到血管紧张素转换酶2（ACE 2）表达增强，提示其在其发病机制中发挥作用，促使本研究。Western blot和免疫荧光法检测ACE 2、Ang 1-7、MAS 1受体（MAS 1-R）、MAPK家族和Akt在结肠中的表达/活性。使用小鼠葡聚糖硫酸钠模型测定外源性施用Ang 1-7或药理学抑制其功能（通过A779处理）的效果。结肠炎诱导后观察到ACE 2、Ang 1 -7和MAS 1-R的结肠表达增强。每日Ang 1-7治疗（0.01-0.06 mg/kg）导致DSS诱导的结肠炎的显著改善。相比之下，每日给予A779显著恶化了结肠炎的特征。Ang 1-7处理可降低结肠炎相关的p38、ERK 1/2和Akt磷酸化。我们的研究结果表明，重要的抗炎作用，血管紧张素1-7在炎症性肠病的发病机制，这可能提供一个未来的治疗策略，以控制疾病的进展。
There is evidence to support a role for angiotensin (Ang) 1–7 in reducing the activity of inflammatory signaling molecules such as MAPK, PKC and SRC. Enhanced angiotensin converting enzyme 2 (ACE2) expression has been observed in patients with inflammatory bowel disease (IBD) suggesting a role in its pathogenesis, prompting this study. The colonic expression/activity profile of ACE2, Ang 1–7, MAS1-receptor (MAS1-R), MAPK family and Akt were determined by western blot and immunofluorescence. The effect of either exogenous administration of Ang 1–7 or pharmacological inhibition of its function (by A779 treatment) was determined using the mouse dextran sulfate sodium model. Enhanced colonic expression of ACE2, Ang1-7 and MAS1-R was observed post-colitis induction. Daily Ang 1–7 treatment (0.01–0.06 mg/kg) resulted in significant amelioration of DSS-induced colitis. In contrast, daily administration of A779 significantly worsened features of colitis. Colitis-associated phosphorylation of p38, ERK1/2 and Akt was reduced by Ang 1–7 treatment. Our results indicate important anti-inflammatory actions of Ang 1–7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.