Department of Obstetrics, Hainan Branch, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Sanya, China.
Kaohsiung J Med Sci. 2024 Oct;40(10):916-925. doi: 10.1002/kjm2.12890. Epub 2024 Sep 4.
This study aims to investigate the effects of the Galectin-3 (Gal-3) inhibitor TD139 on inflammation and the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 pathway in gestational diabetes mellitus (GDM). Human placental tissues were treated with TD139 and TNF-α, assessing Gal-3, ERK/JNK/p38 activation, and inflammatory cytokines. GDM was induced in mice via subcutaneous injections of streptozotocin (STZ). After confirming GDM, mice were treated with 15 mg/kg TD139 on GD 10.5 12.5, 14.5, 16.5, and 18.5. Serum inflammatory cytokines were measured on GD 20.5, and post-delivery placental tissues were analyzed. Data were analyzed using one-way or two-way repeated measures ANOVA with post hoc tests. TD139 suppressed TNF-α-induced increases in Gal-3, IL-1β, IL-6, MCP-1, and ERK/JNK/p38 activation in placental tissues. In STZ-induced GDM mice, TD139 reduced glucose levels, weight loss, and food and water intake. TD139 significantly lowered TNF-α, IL-1β, IL-6, and MCP-1 in serum and placental tissues and inhibited the ERK/JNK/p38 pathway. TD139 improved pup numbers in GDM mice compared to untreated ones. TD139 reduces inflammation and inhibits the ERK/JNK/p38 pathway in TNF-α stimulated placental tissues and STZ-induced GDM mice, suggesting its therapeutic potential for managing GDM-related placental inflammation and improving pregnancy outcomes. The study used TNF-α to mimic GDM in placental tissues and an STZ-induced GDM mouse model, which may not fully represent human GDM complexity. Future research should explore alternative models, and broader signaling pathways, and thoroughly evaluate TD139's safety in pregnancy.
本研究旨在探讨半乳糖凝集素-3（Gal-3）抑制剂 TD139 对妊娠期糖尿病（GDM）中炎症和细胞外信号调节激酶（ERK）/c-Jun N-末端激酶（JNK）/p38 通路的影响。用人胎盘组织处理 TD139 和 TNF-α，评估 Gal-3、ERK/JNK/p38 激活和炎症细胞因子。通过皮下注射链脲佐菌素（STZ）诱导小鼠发生 GDM。在确认 GDM 后，于 GD 10.5、12.5、14.5、16.5 和 18.5 时，用 15mg/kg TD139 对小鼠进行处理。在 GD 20.5 时测量血清炎症细胞因子，并分析产后胎盘组织。使用单向或双向重复测量方差分析（ANOVA）进行数据分析，并进行事后检验。TD139 抑制了 TNF-α诱导的胎盘组织中 Gal-3、IL-1β、IL-6、MCP-1 和 ERK/JNK/p38 激活的增加。在 STZ 诱导的 GDM 小鼠中，TD139 降低了血糖水平、体重减轻以及食物和水的摄入。TD139 显著降低了血清和胎盘组织中的 TNF-α、IL-1β、IL-6 和 MCP-1，并抑制了 ERK/JNK/p38 通路。与未处理组相比，TD139 增加了 GDM 小鼠的幼仔数量。TD139 可降低 TNF-α刺激的胎盘组织和 STZ 诱导的 GDM 小鼠中的炎症，并抑制 ERK/JNK/p38 通路，这表明其在治疗 GDM 相关胎盘炎症和改善妊娠结局方面具有潜在的治疗作用。该研究使用 TNF-α模拟胎盘组织中的 GDM 以及 STZ 诱导的 GDM 小鼠模型，这可能无法完全代表人类 GDM 的复杂性。未来的研究应探索替代模型以及更广泛的信号通路，并彻底评估 TD139 在妊娠中的安全性。
