mRNA levels of myogenic regulatory factors in rat slow and fast muscles regenerating from notexin-induced necrosis

The transcript levels of the myogenic regulatory factors (myoD, myf5, myoge nin and MRF4) were measured by RT PCR in rat soleus (slow) and EDL (fast) m uscles which were regenerating from notexin-induced necrosis. Some muscle f ibers in the EDL were more resistant to the toxin, therefore the necrosis a nd the dominance of myoblasts were delayed for two days in EDL compared to soleus. In spite of this shift in time-course of necrosis, both types of mu scle presented roughly similar, although variable, changes in the expressio n pattern of MRF mRNA levels. For both muscles, the myoD mRNA was upregulat ed on the first day after administration of the toxin, whereas concomitantl y myf-5 mRNA disappeared but showed a substantial increase in later stages of regeneration. In contrast, the mRNA levels of the late MRFs myogenin and MRF4 decreased on day one only in the soleus, then increased on day three in both types of muscle. Meanwhile in EDL the level of MRF4 mRNA remained r elatively normal. Four weeks after administration of the toxin the mRNA lev els for each of the MRFs returned to nearly control levels. This shows that in spite of the different time course of the necrosis and regeneration, al so documented by the microscopical morphology and the skeletal actin mRNA l evels of the muscles, the level of MRF transcripts changed according to a q uite predictable pattern; the upregulation corresponded to myoblast activat ion and the downregulation to the reinnervation. (C) 1998 Elsevier Science B.V. An rights reserved.