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Agrin activates YAP in human skin fibroblast (HSF) through integrin mediated adhesion and Lrp4/MuSK receptor-mediated signaling pathways

Jia Yang, Hongping Ju, Ping Li

Objective: To investigate the effects of agrin on YAP expression in Human Skin Fibroblast (HSF), and the possible mechanism.

Methods: Expression of agrin in HSF was downregulated by siRNA transfection. Migration and invasion ability of HSF was determined by Transwell migration and invasion assay. Expression and phosphorylation levels of agrin, Yes-Associated Protein (YAP), Focal Adhesion Kinase (FAK) and Muscle Associated Receptor Tyrosine kinase (MuSK) were detected by Western blot.

Results: Expression of agrin was significantly downregulated after agrin siRNA transfection (p<0.01). Proliferation, migration and invasion ability of HSF cells was significantly reduced after agrin silencing (p<0.01). No significant differences in total expression levels of YAP, FAK and MuSK were found between cells with or without agrin silencing, while agrin silencing significantly increased phosphorylation level of YAP and significantly reduced phosphorylation level of FAK and MuSK (p<0.01).

Conclusion: Agrin can activate YAP in HSF possibly through the interactions with integrin mediated adhesion and Lrp4/MuSK receptor-mediated signaling pathways.