Send to

Choose Destination
See comment in PubMed Commons below
Cell Signal. 2013 Nov;25(11):2106-14. doi: 10.1016/j.cellsig.2013.06.014. Epub 2013 Jul 2.

Specialization of mitochondrial and vascular oxidant modulated VEGFR in the denervated skeletal muscle.

Author information

Department of Integrative Medicine and Neurobiology, National Key Lab of Medical Neurobiology, Institute of Brain Sciences, Fudan University, Shanghai, China.


Denervation of skeletal muscles results in timely muscular inflammation and muscle-T cell interaction, the cellular events might orchestrate a local circuit involved with IL-1β and IL-15. In the present study, by a combination assay of nerve-muscle preparation, western blot, immuno-precipitation, and radioactive of enzyme activity, we confirmed that mitochondrial and vascular oxidants were considerably up-regulated following gastrocnemius denervation, which was due to gradual decay in mitochondrial biogenesis and XO pathway and accompanied by strengthened IL-1β-VEGFR-2 and IL-15-VEGFR-1 signaling. Intriguingly, these alterations could be triggered by the early established muscular inflammation. In contrast, with prolonged muscle denervation, settings of organelle interconnection were ultimately conveyed by ER bound PTP1B, which promoted VEGFR-1 signaling and contributed to VEGFR-2 activation, and the process could be modulated by mitochondrial and vascular oxidant. Importantly, VEGFR-2 could rescue the disruption of MuSK activity and AchR cluster exerted by IL-1β and IL-15, with PGC-1α and XO involvement. Altogether, extensive network centered on VEGFR-2 signaling was essentially contributed to early recovery processes regarding muscle denervation. Increasing knowledge of this mechanism might open up a conduit for functional response to muscle atrophy, and enable the development of better agents to combat the related disorders.


Mitochondria; Muscle denervation; VEGFR-1; VEGFR-2; XO pathway

[Indexed for MEDLINE]

MeSH terms, Substances

MeSH terms


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center