Unit for Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna, Vienna, Austria; Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH, USA.
Division of Hematology & Oncology, The MetroHealth System and Case Western Reserve University (CWRU), Cleveland, OH, USA.
Cytokine. 2021 Mar;139:155392. doi: 10.1016/j.cyto.2020.155392. Epub 2021 Jan 19.
Cytokines, growth factors or hormones take action through the JAK/STAT5 signaling pathway, which plays a critical role in regulating the intestinal response to infection and inflammation. However, the way in which STAT5 regulates intestinal epithelial compartment is largely ignored due to the lack of genetic tools for proper exploration and because the two STAT5 transcription factors (STAT5A and STAT5B) have some redundant but also distinct functions. In this review article, by focusing on STAT5 functions in the intestinal undifferentiated and differentiated epithelia, we discuss major advances of the growth factor/cytokine-JAK/STAT5 research in view of intestinal mucosal inflammation and immunity. We highlight the gap in the research of the intestinal STAT5 signaling to anticipate the gastrointestinal explorative insights. Furthermore, we address the critical questions to illuminate how STAT5 signaling influences intestinal epithelial cell differentiation and stem cell regeneration during homeostasis and injury. Overall, our article provides a centric view of the relevance of the relationship between chronic inflammatory diseases and JAK/STAT5 pathway and it also gives an example of how chronic infection and inflammation pirate STAT5 signaling to worsen intestinal injuries. Importantly, our review suggests how to protect a wound healing from gastrointestinal diseases by modulating intestinal STAT5.
细胞因子、生长因子或激素通过 JAK/STAT5 信号通路发挥作用，该通路在调节肠道对感染和炎症的反应中起着关键作用。然而，由于缺乏适当探索的遗传工具，以及两个 STAT5 转录因子（STAT5A 和 STAT5B）具有一些冗余但又不同的功能，STAT5 调节肠道上皮细胞隔室的方式在很大程度上被忽视了。在这篇综述文章中，我们通过关注 STAT5 在肠道未分化和分化上皮中的功能，讨论了生长因子/细胞因子-JAK/STAT5 研究在肠道黏膜炎症和免疫方面的主要进展。我们强调了肠道 STAT5 信号研究中的差距，以预测胃肠道探索性的见解。此外，我们还解决了一些关键问题，阐明了 STAT5 信号在稳态和损伤过程中如何影响肠道上皮细胞分化和干细胞再生。总的来说，我们的文章提供了一个关于慢性炎症性疾病与 JAK/STAT5 通路之间关系的核心观点，也提供了一个例子，说明慢性感染和炎症如何劫持 STAT5 信号来加重肠道损伤。重要的是，我们的综述提出了如何通过调节肠道 STAT5 来保护肠道免受胃肠道疾病的影响。
