Inhibition of mammalian muscle differentiation by excretory secretory products of muscle larvae of Trichinella spiralis in vitro
Résumé
The excretory-secretory products (ESP) released
by muscle stage of Trichinella spiralis have been suggested
to be involved in nurse cell formation. However, the molecular
mechanisms by which ESP modulate nurse cell formation
remain unclear. In the present study, the ability of ESP
of muscle larvae of T. spiralis (ML-ESP) to influence the
proliferation and differentiation of murine myoblasts and the
mechanisms were evaluated in vitro using C2C12 myoblast
cell line, which were incubated for various times under grow
or differentiation culture medium containing various concentrations
of ML-ESP. The results indicated that ML-ESP
promoted myoblast proliferation in a dose-dependent manner
and increased the expression of the cell-cycle regulator
cyclin D1 as well as that of proliferating cell nuclear antigen
(PCNA). Conversely, ML-ESP inhibited the differentiation
of these cells, which was evidenced by a reduction in the
levels of MHC and MRFs expression (MyoD and myogenin)
as well as that of p21. In addition, ML-ESP also inhibited the
phosphorylation of p38MAPK in differentiating C2C12 myoblast.
Taken together, these results imply that certain critical
mediators contained in ML-ESP inhibit myogenesis through
enhancing skeletal myoblasts proliferation and downregulating
the expression of MRFs as well as involving p38
MAPK signalling pathway, which provides insight into the
mechanisms utilised by T. spiralis to interfere normal wound
repair in infected muscle cells and affect nurse cell formation.