Placental homing peptide guides HIF1αsilenced exosomes conjugates for targeted enhancement of invasion of trophoblast cells.
Mol Med Rep
; 28(1)2023 Jul.
Article
en En
| MEDLINE
| ID: mdl-37232338
ABSTRACT
There is a current lack of availability of therapeutics to treat Preeclampsia (PE), primarily due to the risk of harm to the fetus. Hypoxiainducible factor1α (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 HIF1αsilenced exosomes to the placenta. HIF1α was overexpressed in JEG3 cells. Then, the glucose uptake, lactate production, proliferation and invasion of HIF1αelevated JEG3 cells were detected. Exosomal membrane protein lysosomeassociated membrane glycoprotein 2b and placental homing peptide CCGKRK gene sequence amplified by PCR were conjugated using short hairpin RNAHIF1α (shHIF1α) sequence (exopepshHIF1α), which were then transfected into MSCs cultured in vitro. Exosomes were isolated from the supernatant of the aforementioned MSCs and identified by determining the size and exosomal markers. Finally, the invasion ability of MSCsderived exosomes treated JEG3 cells were detected using Transwell assays. HIF1α was demonstrated to remarkably promote the uptake of glucose and the production of lactate in JEG3 cells. In addition, high levels of HIF1α facilitated the proliferation of JEG3 cells, while suppressing their invasion ability. Bone marrow derived MSCs were cultured in vitro and exosomes were successfully isolated from these cells. ExopepshHIF1α significantly reduced placental HIF1α expression, and induced significant enhancement of placental invasion. Overall, placental homing peptideguided HIF1αsilenced 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 placentaspecific therapeutic approach.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Preeclampsia
/
MicroARNs
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Exosomas
Tipo de estudio:
Prognostic_studies
Límite:
Female
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Humans
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Pregnancy
Idioma:
En
Revista:
Mol Med Rep
Año:
2023
Tipo del documento:
Article