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Neprilysin participates in skeletal muscle regeneration and is accumulated in abnormal muscle fibres of inclusion body myositis
Author(s) -
Broccolini Aldobrando,
Gidaro Teresa,
Morosetti Roberta,
Gliubizzi Carla,
Servidei Tiziana,
Pescatori Mario,
Tonali Pietro A.,
Ricci Enzo,
Mirabella Massimiliano
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03584.x
Subject(s) - inclusion body myositis , regeneration (biology) , skeletal muscle , neprilysin , anatomy , endocrinology , medicine , chemistry , biology , myositis , microbiology and biotechnology , biochemistry , enzyme
Neprilysin (NEP, EP24.11), a metallopeptidase originally shown to modulate signalling events by degrading small regulatory peptides, is also an amyloid‐β‐ (Aβ) degrading enzyme. We investigated a possible role of NEP in inclusion body myositis (IBM) and other acquired and hereditary muscle disorders and found that in all myopathies NEP expression was directly associated with the degree of muscle fibre regeneration. In IBM muscle, NEP protein was also strongly accumulated in Aβ‐bearing abnormal fibres. In vitro , during the experimental differentiation of myoblasts, NEP protein expression was regulated at the post‐transcriptional level with a rapid increase in the early stage of myoblast differentiation followed by a gradual reduction thereafter, coincident with the progression of the myogenic programme. Treatment of differentiating muscle cells with the NEP inhibitor dl ‐3‐mercapto‐2‐benzylpropanoylglycine resulted in impaired differentiation that was mainly associated with an abnormal regulation of Akt activation. Therefore, NEP may play an important role during muscle cell differentiation, possibly through the regulation, either directly or indirectly, of the insulin‐like growth factor I‐driven myogenic programme. In IBM muscle increased NEP may be instrumental in (i) reducing the Aβ accumulation in vulnerable fibres and (ii) promoting a repair/regenerative attempt of muscle fibres possibly through the modulation of insulin‐like growth factor I‐dependent pathways.