肌球蛋白轻链激酶：治疗炎症性疾病的潜在靶点。
Myosin Light Chain Kinase: A Potential Target for Treatment of Inflammatory Diseases.
作者信息
Xiong Yongjian, Wang Chenou, Shi Liqiang, Wang Liang, Zhou Zijuan, Chen Dapeng, Wang Jingyu, Guo Huishu
机构信息
Central Laboratory, The First Affiliated Hospital, Dalian Medical UniversityDalian, China.
Laboratory Animal Center, Dalian Medical UniversityDalian, China.
出版信息
Front Pharmacol. 2017 May 23;8:292. doi: 10.3389/fphar.2017.00292. eCollection 2017.
Abstract
Myosin light chain kinase (MLCK) induces contraction of the perijunctional apical actomyosin ring in response to phosphorylation of the myosin light chain. Abnormal expression of MLCK has been observed in respiratory diseases, pancreatitis, cardiovascular diseases, cancer, and inflammatory bowel disease. The signaling pathways involved in MLCK activation and triggering of endothelial barrier dysfunction are discussed in this review. The pharmacological effects of regulating MLCK expression by inhibitors such as ML-9, ML-7, microbial products, naturally occurring products, and microRNAs are also discussed. The influence of MLCK in inflammatory diseases starts with endothelial barrier dysfunction. The effectiveness of anti-MLCK treatment may depend on alleviation of that primary pathological mechanism. This review summarizes evidence for the potential benefits of anti-MLCK agents in the treatment of inflammatory disease and the importance of avoiding treatment-related side effects, as MLCK is widely expressed in many different tissues.
摘要
肌球蛋白轻链激酶（MLCK）响应肌球蛋白轻链的磷酸化，诱导连接周缘顶端肌动球蛋白环收缩。在呼吸系统疾病、胰腺炎、心血管疾病、癌症和炎症性肠病中均观察到MLCK的异常表达。本综述讨论了MLCK激活和引发内皮屏障功能障碍所涉及的信号通路。还讨论了通过ML-9、ML-7等抑制剂、微生物产物、天然产物和微小RNA调节MLCK表达的药理作用。MLCK在炎症性疾病中的影响始于内皮屏障功能障碍。抗MLCK治疗的有效性可能取决于该主要病理机制的缓解。本综述总结了抗MLCK药物在治疗炎症性疾病中潜在益处的证据，以及避免治疗相关副作用的重要性，因为MLCK在许多不同组织中广泛表达。
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