Journal of Clinical & Experimental Pharmacology

Abstract

Distinctive VEGFR2 Endocytic Delivery during Muscle Mobilization

Han-Wei Huang,Hui Zhao*

Denervation of skeletal muscles initiates a cascade of cellular events that can lead to muscle atrophy, however, the underlying mechanism is controversial. In the present study, by using techniques including real-time PCR, immunoblotting, fluorescent in situ hybridization, and enzyme-linked immunosorbent, we demonstrated that VEGFR2 was distinctively cross-linked with MyHCI in gastrocnemius, and MyHC2B in soleus, which was likely responsible for activation of receptor tyrosine kinases including growth factor receptor-bound 2, phospholipase Cγ, p85, Vav, and human epidermal growth factor receptor 2. When challenged with muscle mobilization, in gastrocnemius, VEGFR2 was preferentially translocated into mitochondria, which resulted in activation of NAD+ - SIRT1 and remodel of macrophage polarization. Alternatively, in soleus, VEGFR2 was targeted to ER, this shortrange transport eventually enhanced T cell activation including miR181a expression and IL-15 release. Importantly, M1 macrophage polarization and T cell activation mostly induced disrupted muscular homeostasis, the cellular processes might make soleus more vulnerable to insults than gastrocnemius. Therefore, endocytic delivery of VEGFR2 by myosin might precipitate distinctive cellular environment in the mobilized gastrocnemius and soleus, mitochondrial gene transcription and T cell activation were proposed to involve in the phenotype-dependent alterations respectively.