Albuayjan Haya Hamed Hassan, Watanabe Mayu, Sugawara Ryosuke, Katsuyama Eri, Mise Koki, Oi Yukiko, Kanno Ayaka, Yang BoXuan, Tahara Toshihisa, Nojima Ichiro, Nakatsuka Atsuko, Eguchi Jun, Maki Jota, Eto Eriko, Hayata Kei, Masuyama Hisashi, Wada Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
Faculty of Health Science, Okayama University Medical School, Graduate School of Health Sciences, Okayama University, Okayama, Japan.
Sci Rep. 2025 May 30;15(1):18981. doi: 10.1038/s41598-025-03879-8.
Galectin-9 (Gal-9) is highly expressed in trophoblasts in placenta. Interaction between Gal-9 and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) is important for the differentiation of tissue resident natural killer (trNK) cells in placenta and maintenance of normal pregnancy. Furthermore, the enhanced maternal systemic inflammation associated with increased proinflammatory cytokines in preeclampsia is mediated by enhanced interaction between Gal-9 and Tim-3. However, the role of Gal-9 in gestational diabetes (GDM) remains unexplored. Plasma Gal-9 levels were elevated at 3rd trimester in pregnant women with GDM and positively correlated with placenta and newborn weight. Lgals9 knockout pregnant mice fed with high fat diet (HFD KO) demonstrated maternal glucose intolerance and fetus macrosomia compared with controls (HFD WT). In HFD KO, increased proliferating cells, reduced apoptosis, and autophagy impairment were observed in junctional zones. The number of trNK cells and percentage of Tim-3 + trNK increased, while early apoptosis percentage in Tim-3 + trNK was reduced in placenta of HFD KO. The elevation of plasma Gal-9 may be a biomarker for prediction of maternal glucose intolerance and fetal macrosomia in pregnant women with GDM and Gal-9 functions as a compensation factor for GDM by inducing apoptosis in Tim-3 + trNK cells.
半乳糖凝集素-9（Gal-9）在胎盘的滋养层细胞中高表达。Gal-9与含T细胞免疫球蛋白和粘蛋白结构域-3（Tim-3）之间的相互作用对于胎盘中组织驻留自然杀伤（trNK）细胞的分化以及维持正常妊娠至关重要。此外，子痫前期中与促炎细胞因子增加相关的母体全身炎症增强是由Gal-9与Tim-3之间增强的相互作用介导的。然而，Gal-9在妊娠期糖尿病（GDM）中的作用仍未得到探索。GDM孕妇在孕晚期血浆Gal-9水平升高，且与胎盘和新生儿体重呈正相关。与对照组（高脂饮食野生型，HFD WT）相比，高脂饮食喂养的Lgals9基因敲除怀孕小鼠（高脂饮食基因敲除型，HFD KO）表现出母体葡萄糖不耐受和胎儿巨大儿。在HFD KO小鼠中，在连接区观察到增殖细胞增加、细胞凋亡减少和自噬受损。HFD KO小鼠胎盘trNK细胞数量和Tim-3⁺ trNK细胞百分比增加，而Tim-3⁺ trNK细胞的早期凋亡百分比降低。血浆Gal-9升高可能是预测GDM孕妇母体葡萄糖不耐受和胎儿巨大儿的生物标志物，并且Gal-9通过诱导Tim-3⁺ trNK细胞凋亡而作为GDM的一种补偿因子发挥作用。
