Upregulation of IL-15 in the placenta alters trophoblasts behavior contributing to gestational diabetes mellitus
Jiaqi Li, Yuan Li, Xuan Zhou, Lijie Wei, Jingyi Zhang, Shenglan Zhu, Huiting Zhang, Xuan Gao, Lali Mwamaka Sharifu, Shaoshuai Wang, Ling Xi, Ling Feng
Abstract
BACKGROUND: Interleukin-15 (IL-15), a member of the 'four α-helix bundle' cytokine family, has been associated with many inflammatory and metabolic diseases. Abnormal expression of IL-15 has been linked to the occurrence and development of obesity and diabetes. However, there is a paucity of research on the involvement of IL-15 in Gestational Diabetes Mellitus (GDM). This study aims at investigating the role of IL-15 in the pathogenesis of GDM. RESULTS: IL-15 was consistently expressed in the placenta throughout pregnancy and dynamically changed with pregnancy progress. Trophoblasts have been identified as the major source of IL-15 in the placenta. Expression of IL-15 was significantly increased in the placenta of GDM and in the trophoblasts cultured with high glucose (HG). In our study, expression of IL-15 in the placenta was positively correlated with blood glucose concentration of 75 g Oral Glucose Tolerance Test (OGTT), and was inversely correlated with weight of newborns. Further investigations in vitro showed that exogenous addition of IL-15 promoted trophoblasts proliferation, improved invasion and tube formation ability by activating the JAK/STAT signaling pathway, which be blocked by JAK inhibitors. CONCLUSION: Our results demonstrated that IL-15 expression in the placenta was dynamically changing during pregnancy, and it was upregulated in the placenta of GDM patients. Furthermore, IL-15 altered the biological behavior of trophoblasts through JAK/STAT signaling pathway in vitro, and may contributed to the placental pathology of GDM. Our findings provide a new direction for studying the pathophysiological changes of placenta in GDM.