Glial cell line‐derived neurotrophic factor and basic fibroblast growth factor derived from skeletal muscle pericytes increase the barrier function of endothelial cells in the endomysium

Abstract

AbstractObjectivesIn skeletal muscle, the capillaries have tight junctions (TJs) that are structurally similar to those in the blood‐brain barrier (BBB) and blood‐nerve barrier (BNB). Although the endomysial capillaries include endothelial cells and pericytes, the properties of the endomysial pericytes have not been well elucidated. The purpose of this study was to establish a human skeletal muscle pericyte cell (HSMPCT) line, and examine whether the established cell line has similar properties to pericytes from the BBB and BNB.MethodHSMPCTs were isolated and introduced with retroviruses harboring temperature‐sensitive SV40 T antigen and telomerase genes. Then, we examined whether this cell line modifies the barrier function of a human skeletal muscle microvascular endothelial cell line, TSM15.ResultsA new HSMPCT cell line was successfully established. The conditioned media (CM) from HSMPCTs increased the transendothelial electrical resistance of the TSM15 cells and decreased permeability to 10kD‐dextran. Glial cell line‐derived neurotrophic factor (GDNF) and basic fibroblast growth factor (bFGF) increased the barrier function of TSM15 cells. The CM of HSMPCTs with anti‐GDNF or anti‐bFGF antibodies attenuated the effect of upregulating the barrier function of TSM15 cells. These results indicate that soluble factors, such as GDNF and bFGF, released from HSMPCTs strengthen the barrier function of TSM15 cells.ConclusionGDNF and bFGF released from HSMPCTs increase the barrier function of endomysial endothelium. These HSMPCTs and TSM15 cells, which are recognized as an in vitro model of the endomysial capillary, might facilitate the analysis of the pathophysiology of the microvasculature in human skeletal muscle.