Placental homing peptide guides HIF1α‑silenced exosomes conjugates for targeted enhancement of invasion of trophoblast cells.

Abstract

There is a current lack of availability of therapeutics to treat Preeclampsia (PE), primarily due to the risk of harm to the fetus. Hypoxia‑inducible factor‑1α (HIF1α) is highly expressed in trophoblast cells and suppresses their invasive ability. Extensive studies have confirmed the positive effects of mesenchymal stem cell (MSC)‑derived exosomes on PE. The aim of the present study was to develop a method for targeted delivery of HIF1α‑silenced exosomes to the placenta. HIF1α was overexpressed in JEG‑3 cells. Then, the glucose uptake, lactate production, proliferation and invasion of HIF1α‑elevated JEG‑3 cells were detected. Exosomal membrane protein lysosome‑associated membrane glycoprotein 2b and placental homing peptide CCGKRK gene sequence amplified by PCR were conjugated using short hairpin RNA‑HIF1α (sh‑HIF1α) sequence (exo‑pep‑sh‑HIF1α), which were then transfected into MSCs cultured invitro. Exosomes were isolated from the supernatant of the aforementioned MSCs and identified by determining the size and exosomal markers. Finally, the invasion ability of MSCs‑derived exosomes treated JEG‑3 cells were detected using Transwell assays. HIF1α was demonstrated to remarkably promote the uptake of glucose and the production of lactate in JEG‑3 cells. In addition, high levels of HIF1α facilitated the proliferation of JEG‑3 cells, while suppressing their invasion ability. Bone marrow derived MSCs were cultured invitro and exosomes were successfully isolated from these cells. Exo‑pep‑sh‑HIF1α significantly reduced placental HIF1α expression, and induced significant enhancement of placental invasion. Overall, placental homing peptide‑guided HIF1α‑silenced exosomes effectively facilitated the invasion of placental trophoblasts, which could be used for the targeted delivery of payloads to the placenta and serve as a novel placenta‑specific therapeutic approach.