Song X, Wang C T, Geng X H
Department of ICU, Shengli Hospital of Shandong University, Shandong, China.
Department of ICU, Dong E People's Hospital, Shandong, China.
Genet Mol Res. 2015 Oct 29;14(4):13746-53. doi: 10.4238/2015.October.28.37.
Sepsis is a major cause of morbidity and mortality in critically ill patients. The sepsis syndrome results from a dysregulated inflammatory response to infection that leads to multiple-organ failure, but the underlying mechanisms remain poorly understood. More and more reports show that microRNAs (miRNAs) play an important role in sepsis. In the progression of this syndrome, cells change their behavior in response to cytokines stimulated by sepsis, such as interleukin-10 (IL-10). IL-10 can activate JAK2-STAT3 in the cells to protect them from damage. miR-29a is a potential miRNA directly targeting STAT3. In this study, we investigate the role of miR-29a in targeting STAT3 during sepsis. When cells were treated with IL-10, STAT3 was activated in monocytes, as determined using western blotting. It was verified that STAT3 was a new target gene of miR-29a. miR-29a could inhibit IL-10-induced cytokine release by targeting JAK-STAT3 in monocytes. In conclusion, this study demonstrates for the first time that miR-29a inhibits STAT3 in human monocytes during sepsis.
脓毒症是重症患者发病和死亡的主要原因。脓毒症综合征源于对感染的炎症反应失调,进而导致多器官功能衰竭,但其潜在机制仍知之甚少。越来越多的报告表明,微小RNA(miRNA)在脓毒症中起重要作用。在该综合征的进展过程中,细胞会因脓毒症刺激的细胞因子(如白细胞介素-10,IL-10)而改变其行为。IL-10可激活细胞中的JAK2-STAT3以保护细胞免受损伤。miR-29a是一种直接靶向STAT3的潜在miRNA。在本研究中,我们调查了miR-29a在脓毒症期间靶向STAT3的作用。当用IL-10处理细胞时,通过蛋白质印迹法测定发现单核细胞中的STAT3被激活。证实STAT3是miR-29a的一个新靶基因。miR-29a可通过靶向单核细胞中的JAK-STAT3抑制IL-10诱导的细胞因子释放。总之,本研究首次证明脓毒症期间miR-29a在人单核细胞中抑制STAT3。