The mechanosensitive transmembrane receptor NRP1 transduces mechanical stress inhibition via LATS1/YAP in hypertrophic scars

Abstract

Abstract A hypertrophic scar (HS) is abnormal fibrous hyperplasia of the skin caused by excessive tissue repair in response to skin burns and trauma, which restricts physical function and impairs the quality of life of patients. Mechanobiological components play an essential role in wound healing and scar formation and can improve the efficiency therapy. Herein, we used weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEGs) analysis to screen the neuropilin 1 (NRP1) gene which is sensitive to mechanical stress in various human cells. We confirmed that mechanical stress stimulates NRP1 expression in human HS endothelial cells. Immunostaining revealed that the expression of large tumor suppressor kinase 1 (LATS1) and yes-associated protein (YAP) is mediated by mechanical compression. We verified the effects of mechanical stress on NRP1, LATS1, and YAP expressions in pressure culture human dermal microvascular endothelial cell model and rat tail-scar model. We knocked down NRP1 using NRP1-shRNA and validated that NRP1 reduced YAP expression by regulating the YAP upstream regulator LATS1. Co-immunoprecipitation analysis indicated that NRP1 binds to YAP and that mechanical compression disrupted this binding. Collectively, our results indicated that the mechanosensitive transmembrane receptor NRP1 transduces mechanical force inhibition by inhibiting YAP expression. Strategies targeting NRP1 may promote compression therapy with optimal and comfortable pressures.