SOX18 promotes lymphatic vessel regeneration to alleviate lymphedema by upregulating PROX1.

Abstract

Promoting lymphatic vessel regeneration is an important method for repairing lymphedema. SOX18 can regulate lymphatic vessel development and plays a crucial role in promoting lymphatic vessel generation. This study aims to demonstrate the role of SOX18 in regulating lymphatic vessel regeneration for the repair of lymphedema and explore its related molecular mechanism. We used classical molecular biology methods such as RT-qPCR, Western blotting, CCK8 assay, Transwell assay, immunofluorescence, tube formation assay, dual luciferase assay, and CHIP assay to investigate the role of overexpressed SOX18 in promoting lymphatic vessel regeneration and its related molecular regulatory mechanisms. Subsequently, pathological histological analysis, Western blotting, and immunofluorescence were used to study the lymphedema mouse model. Overexpression of SOX18 promoted the proliferation, migration, and tube formation of LECs in vitro. Overexpression of SOX18 promoted lymphatic vessel regeneration for the repair of lymphedema in vivo. Mechanistically, SOX18 bound to the PROX1 promoter, promoted PROX1 transcription, activated the ERK pathway, upregulated VEGFR3, and promoted lymphatic vessel regeneration. This study demonstrates the important role of overexpressed SOX18 in regulating lymphatic vessel regeneration for the repair of lymphedema, which may provide new therapeutic options for lymphedema treatment.