Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
Clin Chim Acta. 2011 Mar 18;412(7-8):513-20. doi: 10.1016/j.cca.2010.12.020. Epub 2010 Dec 23.
The mammalian family of mitogen-activated protein kinases (MAPKs) is activated by diverse extracellular and intracellular stimuli, and thereby they play an essential role in connecting cell-surface receptors to changes in transcriptional programs. The MAPK signaling pathways regulate a wide range of cellular activities and have been implicated in the pathogenesis of several diseases, including inflammatory bowel disease (IBD). This review summarizes recent findings on the regulatory mechanism of MAPK signaling pathways, focusing on nuclear targets and their role in IBD. Finally, it summarizes how these signaling pathways have been exploited for the development of therapeutics and discuss the current knowledge of potential MAPK inhibitors and their anti-inflammatory effects in clinical trials related to IBD.
哺乳动物丝裂原活化蛋白激酶（MAPK）家族通过多种细胞外和细胞内刺激激活，从而在连接细胞表面受体与转录程序变化方面发挥重要作用。MAPK 信号通路调节广泛的细胞活动，并与几种疾病的发病机制有关，包括炎症性肠病（IBD）。本综述总结了 MAPK 信号通路的调控机制的最新发现，重点介绍了核靶点及其在 IBD 中的作用。最后，总结了这些信号通路在治疗药物开发中的应用，并讨论了与 IBD 相关的临床试验中潜在的 MAPK 抑制剂及其抗炎作用的现有知识。
