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Active hepatocyte growth factor is present in skeletal muscle extracellular matrix
Author(s) -
Tatsumi Ryuichi,
Allen Ronald E.
Publication year - 2004
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.20114
Subject(s) - hepatocyte growth factor , skeletal muscle , extracellular , extracellular matrix , proteases , chemistry , microbiology and biotechnology , medicine , endocrinology , biochemistry , biology , enzyme , receptor
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. Muscle Nerve, 2004