Role of galectin-9 in the development of gestational diabetes mellitus
Abstract 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....
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Nature Portfolio
2025-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-025-03879-8 |
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| author | Haya Hamed Hassan Albuayjan Mayu Watanabe Ryosuke Sugawara Eri Katsuyama Koki Mise Yukiko Oi Ayaka Kanno BoXuan Yang Toshihisa Tahara Ichiro Nojima Atsuko Nakatsuka Jun Eguchi Jota Maki Eriko Eto Kei Hayata Hisashi Masuyama Jun Wada |
| author_facet | Haya Hamed Hassan Albuayjan Mayu Watanabe Ryosuke Sugawara Eri Katsuyama Koki Mise Yukiko Oi Ayaka Kanno BoXuan Yang Toshihisa Tahara Ichiro Nojima Atsuko Nakatsuka Jun Eguchi Jota Maki Eriko Eto Kei Hayata Hisashi Masuyama Jun Wada |
| author_sort | Haya Hamed Hassan Albuayjan |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-c2866ed1e6594a4bbfc122a79b14ef55 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-c2866ed1e6594a4bbfc122a79b14ef552025-08-20T02:00:12ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-03879-8Role of galectin-9 in the development of gestational diabetes mellitusHaya Hamed Hassan Albuayjan0Mayu Watanabe1Ryosuke Sugawara2Eri Katsuyama3Koki Mise4Yukiko Oi5Ayaka Kanno6BoXuan Yang7Toshihisa Tahara8Ichiro Nojima9Atsuko Nakatsuka10Jun Eguchi11Jota Maki12Eriko Eto13Kei Hayata14Hisashi Masuyama15Jun Wada16Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAbstract 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.https://doi.org/10.1038/s41598-025-03879-8 |
| spellingShingle | Haya Hamed Hassan Albuayjan Mayu Watanabe Ryosuke Sugawara Eri Katsuyama Koki Mise Yukiko Oi Ayaka Kanno BoXuan Yang Toshihisa Tahara Ichiro Nojima Atsuko Nakatsuka Jun Eguchi Jota Maki Eriko Eto Kei Hayata Hisashi Masuyama Jun Wada Role of galectin-9 in the development of gestational diabetes mellitus Scientific Reports |
| title | Role of galectin-9 in the development of gestational diabetes mellitus |
| title_full | Role of galectin-9 in the development of gestational diabetes mellitus |
| title_fullStr | Role of galectin-9 in the development of gestational diabetes mellitus |
| title_full_unstemmed | Role of galectin-9 in the development of gestational diabetes mellitus |
| title_short | Role of galectin-9 in the development of gestational diabetes mellitus |
| title_sort | role of galectin 9 in the development of gestational diabetes mellitus |
| url | https://doi.org/10.1038/s41598-025-03879-8 |
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