Zhao Fei, Liu Xinhong, Qin Hong
Department of Obstetrics and Gynecology, Shenzhen Longhua District Maternal and Child Health Hospital, No. 68, Huawang Road, Longhua District, Shenzhen, 570105, China.
Hereditas. 2025 Aug 28;162(1):176. doi: 10.1186/s41065-025-00542-0.
Gestational diabetes mellitus (GDM) is considered the most common complication of pregnancy, and is a very dangerous disease for both mother and baby. Homeobox A13 (HOXA13) has been discovered to join into some diseases through exhibiting regulatory functions. Importantly, hypermethylation of HOXA13 has been observed in the placental tissues of preeclampsia. However, the regulatory impacts of HOXA13 on GDM progression keep dimness.
The GDM cell model and GDM rat model were established. The expressions of genes were measured through RT-qPCR, western blot or IHC assay. The cell proliferation was tested through MTT and Edu assays. The cell migration was determined through Transwell assay. The fasting blood glucose of rats was detected through the blood glucose meter.
HOXA13 was verified to be lowly expressed in placental tissues from GDM patients. In addition, the cell proliferation and migration abilities of trophoblast cells were attenuated after high glucose (HG) treatment, but these impacts were counteracted after HOXA13 overexpression. It was further demonstrated that HOXA13 affected the proliferation and migration abilities of HG-triggered trophoblast cells by enhancing smad2 expression. At last, it was testified that HOXA13 can ameliorate GDM symptoms in vivo.
This study manifested that HOXA13 accelerated HG-triggered trophoblast cell growth and migration by regulating the smad2 pathway. This discovery hinted that HOXA13 may be a target for ameliorating GDM.
妊娠期糖尿病（GDM）被认为是最常见的妊娠并发症，对母婴来说都是非常危险的疾病。已发现同源框A13（HOXA13）通过发挥调节功能参与某些疾病的发生。重要的是，子痫前期患者胎盘组织中观察到HOXA13的高甲基化。然而，HOXA13对GDM进展的调节作用仍不清楚。
建立GDM细胞模型和GDM大鼠模型。通过RT-qPCR、蛋白质免疫印迹或免疫组化分析检测基因表达。通过MTT和Edu分析检测细胞增殖。通过Transwell分析测定细胞迁移。通过血糖仪检测大鼠空腹血糖。
证实HOXA13在GDM患者胎盘组织中低表达。此外，高糖（HG）处理后滋养层细胞的增殖和迁移能力减弱，但HOXA13过表达后这些影响被抵消。进一步证明HOXA13通过增强smad2表达影响HG诱导的滋养层细胞的增殖和迁移能力。最后，证实HOXA13可在体内改善GDM症状。
本研究表明HOXA13通过调节smad2途径促进HG诱导的滋养层细胞生长和迁移。这一发现提示HOXA13可能是改善GDM的一个靶点。
