Autophagy plays an essential role in gestational diabetes mellitus (GDM). Death-associated protein kinase-3 (DAPK3) regulates a variety of cellular functions; however, the relationship between DAPK3 and autophagy is unknown. In this study, we aim to investigate whether DAPK3 is associated with autophagy in GDM, and we found that DAPK3 was upregulated in the placenta of GDM patients and extravillous trophoblast cells under high-glucose conditions. Silencing DAPK3 decreased the assembly of the STX17-SNAP29-VAMP8 complex, leading to the blockade of autophagosome-lysosome fusion by mediating synaptosomal-associated protein 29 (SNAP29). Moreover, knockdown of DAPK3 ameliorates cell invasion and mediates autophagy in high glucose, and does not alter the expression of autophagy-related genes in normal glucose. Our study demonstrates the significance of DAPK3 in autophagy and GDM, which may provide new insights into the molecular mechanisms regulating trophoblast invasion.

中文翻译：

---

沉默的DAPK3通过在高葡萄糖处理下在滋养细胞中介导SNAP29来阻止自噬体-溶酶体融合。

自噬在妊娠糖尿病（GDM）中起着至关重要的作用。死亡相关蛋白激酶3（DAPK3）调节多种细胞功能。但是，DAPK3与自噬之间的关系尚不清楚。在这项研究中，我们旨在研究DAPK3是否与GDM中的自噬有关，并且我们发现在高葡萄糖条件下，GAPK患者的胎盘和绒毛外滋养层细胞中的DAPK3被上调。沉默DAPK3减少了STX17-SNAP29-VAMP8复合物的装配，通过介导突触体相关蛋白29（SNAP29）导致自噬体-溶酶体融合的阻断。此外，DAPK3的敲低改善了细胞侵袭并介导了高糖中的自噬，并且不会改变正常葡萄糖中自噬相关基因的表达。