JAK-STAT细胞信号转导通路与急性胰腺炎关系的研究进展

JAK-STAT signaling pathway and acute pancreatitis

急性胰腺炎(acute pancreatitis,AP)的发病机制长期以来是医学界研究的一个重要课题.AP时,细胞因子、生长因子等与酪氨酸蛋白激酶(Janus kinase,JAK)相关受体结合而激活JAKs,活化的JAKs使受体链酪氨酸残基磷酸化,而处于下游的信号转导-转录活化因子(signal transducers and activators of transcription,STAT)与受体复合物酪氨酸磷酸化的特异位点结合,此时JAKs接近STATs并使STATs活化,活化的STATs与受体分离,转移到细胞核内,调控调控Bcl-2、Bcl-X(L)及Mcl-1等基因表达,从而参与胰腺炎的发病机制,而通过STATs脱磷酸化可终止信号的转导.目前越来越多临床实验和动物研究表明JAK-STAT通路与AP有密切相关.现就JAK-STAT信号通路的结构、分布、功能及介导AP发病机制作一综述.

The pathogenesis of acute pancreatitis has long been an important research topic. In acute pancreatitis, cytokines and growth factors bind to Janus kinase （JAK） related receptors, and activate JAKs. The activated JAKs phosphorylate the tyrosine residues of the receptor. The downstream signal transducers and activators of transcription （STAT） then bind to the specific site of the phosphorylated JAK receptor complexes, leading to the activation of STATs. The activated STATs detach from the receptor complexes and translocate to the nucleus to regulate the expression of Bcl-2, Bcl-X（L）, Mcl-1 and other genes, thereby participating in the pathogenesis of pancreatitis. Such signal transduction can be terminated by the dephosphorylation of STATs. At present, more and more clinical experiments and animal studies have shown that the JAK- STAT pathway is closely related with acute pancreatitis. In this article, we will review the structure, distribution, and function of JAK-STAT signaling pathway as well as the role of JAK- STAT signaling pathway in the pathogenesis of acute pancreatitis.