Active hepatocyte growth factor is present in skeletal muscle extracellular matrix

Ryuichi Tatsumi, Ronald E. Allen

    Research output: Contribution to journalArticlepeer-review

    78 Scopus citations

    Abstract

    When skeletal muscle is stretched or injured, satellite cells are activated to proliferate, and this process can be mediated by release of the active form of hepatocyte growth factor (HGF) from the extracellular matrix. The objective of these experiments was to determine whether the mechanism of release includes proteolytic activation of pro-HGF. Extracellular HGF in uninjured adult rat extensor digitorum longus muscle was extracted by treatment with 1 M NaCl or heparinases I and III in the presence of a cocktail of serine protease inhibitors. Active HGF heterodimer was the predominant form present, but both pro-HGF and active HGF were extracted when muscle was incubated with Triton X-100 or crush-injured. Incubation of exogenous pro-HGF with uninjured or crush-injured skeletal muscle resulted in cleavage to the active form, indicating that endogenous extracellular proteases are present and capable of rapidly converting pro-HGF to active HGF. Finally, treatment with sodium nitroprusside, a nitric oxide (NO) donor, resulted in liberation of active HGF. These experiments indicate that the active form of HGF is present in the extracellular compartment of uninjured skeletal muscle; therefore, the mechanism of HGF release in response to stretch and NO does not require proteolytic activation of pro-HGF.

    Original languageEnglish (US)
    Pages (from-to)654-658
    Number of pages5
    JournalMuscle and Nerve
    Volume30
    Issue number5
    DOIs
    StatePublished - Nov 2004

    Keywords

    • Extracellular matrix
    • Hepatocyte growth factor
    • Muscle
    • Proteolysis

    ASJC Scopus subject areas

    • Physiology
    • Clinical Neurology
    • Cellular and Molecular Neuroscience
    • Physiology (medical)

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