Milan K L, Nandhana Nambi, Shree R Adhi, Leela R, Jahnavi S, Anuradha M, Ramkumar Kunka Mohanram
Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur 603 203 Tamil Nadu, India.
Department of Obstetrics & Gynaecology, SRM Medical College Hospital and Research Centre, Kattankulathur 603203 Tamil Nadu, India.
Hum Immunol. 2025 Jul;86(4):111331. doi: 10.1016/j.humimm.2025.111331. Epub 2025 May 27.
Gestational Diabetes Mellitus (GDM) is characterized by impaired glucose metabolism and insulin resistance affecting up to 14.7 % of pregnancies. GDM is associated with adverse perinatal outcomes and long-term health risks for the offspring, including obesity and type 2 diabetes (T2DM). Maternal inflammation plays a key role in driving these complications, aggravating metabolic disturbances, and contributing to adverse developmental programming. In recent years, inflammasomes have emerged as the key regulators of inflammation. This study hypothesizes that NEK7 activates the inflammasomes in GDM pathogenesis. PCR analysis revealed that NEK7 expression, along with NLRP1 and NLRP3, was significantly overexpressed in pregnant women with GDM (n = 20) when compared to healthy pregnant women (n = 20). Further, a positive correlation was observed between NEK7 and the expression of NLRP1 and NLRP3, suggesting a potential mechanistic link in the regulation of inflammation in GDM. Additionally, the expression levels of NLRP1 and NLRP3 were found to strongly correlate with BMI, fasting glucose, postprandial glucose, HOMA-IR, and HbA1c levels in GDM patients. Furthermore, inflammatory cytokines, including IL-1β, IL-18, IL-6, and TNF-α, were significantly upregulated in GDM patients and positively correlated with the expression, suggesting the regulation of inflammation through inflammasomes. To validate the hypothesis, BeWo cells were cultured in a hyperglycemic environment. The results demonstrated that NEK7, along with inflammasomes and inflammatory cytokines, were significantly overexpressed in BeWo cells exposed to high glucose. Collectively, this study suggests that NEK7 upregulation may trigger inflammasome activation, contributing to the pathogenesis of GDM. These findings highlight the need for further research to develop the therapeutic approaches that target NEK7 to mitigate inflammation in GDM.
妊娠期糖尿病（GDM）的特征是葡萄糖代谢受损和胰岛素抵抗，影响高达14.7%的妊娠。GDM与围产期不良结局以及后代的长期健康风险相关，包括肥胖和2型糖尿病（T2DM）。母体炎症在引发这些并发症、加剧代谢紊乱以及导致不良发育编程方面起着关键作用。近年来，炎性小体已成为炎症的关键调节因子。本研究假设NEK7在GDM发病机制中激活炎性小体。PCR分析显示，与健康孕妇（n = 20）相比，GDM孕妇（n = 20）中NEK7的表达以及NLRP1和NLRP3的表达均显著上调。此外，观察到NEK7与NLRP1和NLRP3的表达之间存在正相关，提示在GDM炎症调节中存在潜在的机制联系。另外，发现GDM患者中NLRP1和NLRP3的表达水平与BMI、空腹血糖、餐后血糖、HOMA-IR和HbA1c水平密切相关。此外，包括IL-1β、IL-18、IL-6和TNF-α在内的炎性细胞因子在GDM患者中显著上调，且与表达呈正相关，表明通过炎性小体调节炎症。为了验证这一假设，将BeWo细胞在高血糖环境中培养。结果表明，在暴露于高糖的BeWo细胞中，NEK7以及炎性小体和炎性细胞因子均显著上调。总体而言，本研究表明NEK7上调可能触发炎性小体激活，促成GDM的发病机制。这些发现凸显了进一步研究以开发靶向NEK7减轻GDM炎症的治疗方法的必要性。
