Lymphangiogenic responses of lymphatic endothelial cells to steady direct-current electric fields

Linbo Guan; Ping Fan; Yufeng Wang; Xinghui Liu; Rui Liu; Wandi Ma; Huai Bai

doi:10.1080/19336918.2023.2271260

Lymphangiogenic responses of lymphatic endothelial cells to steady direct-current electric fields

Cell Adh Migr. 2023 Dec;17(1):1-14. doi: 10.1080/19336918.2023.2271260. Epub 2023 Oct 27.

Authors

Linbo Guan¹, Ping Fan¹, Yufeng Wang¹, Xinghui Liu², Rui Liu³, Wandi Ma¹, Huai Bai¹

Affiliations

¹ Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China.
² Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.
³ Division of Peptides Related with Human Disease, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Lymphangiogenesis plays pivotal roles in diverse physiological and pathological conditions. Steady direct-current electric fields (DC EFs) induce vascular endothelial behaviors related to angiogenesis have been observed. This study investigated the effects of DC EFs on the lymphangiogenic response of lymphatic endothelial cells (LECs). We demonstrated that EFs stimulation induced directional migration, reorientation, and elongation of human LECs in culture. These lymphangiogenic responses required VEGF receptor 3 (VEGFR-3) activation and were mediated through the PI3K-Akt, Erk1/2, and p38 MAPK signaling pathways in relation to the reorganization of the actin cytoskeleton. Our results indicate that endogenous EFs may play a role in lymphangiogenesis in vivo, and VEGFR-3 signaling activation may be involved in the cellular function of LECs driven by EFs.

Keywords: Alignment; cell migration; electrical stimulation; lymphangiogenesis; lymphatic endothelial cells; orientation; signal transduction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Endothelial Cells / metabolism
Humans
Lymphangiogenesis*
Phosphatidylinositol 3-Kinases / metabolism
Signal Transduction
Vascular Endothelial Growth Factor Receptor-3* / metabolism
Vascular Endothelial Growth Factor Receptor-3* / pharmacology

Substances

Vascular Endothelial Growth Factor Receptor-3
Phosphatidylinositol 3-Kinases

Grants and funding

This work was supported by the National Natural Science Foundation of China 81471462 and 81271733, Sichuan Province Science and Research foundation of China 2019YFS0316. Program for Changjiang Scholars and Innovative Research Team in University IRT0935, the Fundamental Research Funds for the Central Universities, and Research Seed Fund from West China Second University Hospital of Sichuan University.