A myogenic regulatory gene, qmf1, is expressed by adult myonuclei after injury

Abstract

Myogenic regulatory factors (MRFs) induce differentiation in developing muscle. We examined the role of MRFs in the repair of adult muscle using a model of stretch-induced injury in 5-wk-old chickens. The anterior latissimus dorsi muscle was stretched by loading the wing with 10% of body weight, while the contralateral muscle served as a control. At various intervals (0.5-72 h), chickens were killed by CO2 asphyxiation and the muscles were frozen. Slot hybridizations showed that the onset of high qmf1 expression occurred as early as 0.5 h, which was before regenerative processes involving satellite cell proliferation were observed. Maximal qmf1 expression varied among animals from 3 to 16 h and returned to control levels by 72 h. Within a muscle, in situ hybridization showed that maximal qmf1 expression varied spatially with > 60% of the nuclei within active fascicles being positive. We interpret this high percentage to mean that many of the nuclei of preexisting muscle fibers must be expressing qmf1. The expression of the protooncogene c-myc (presumably by proliferating cells such as satellite cells, fibroblasts, and capillary epithelial cells) and the MRF qmf1 (by myoblasts and adult muscle nuclei) are among the early molecular responses of injured muscle. We conclude that myogenic regulatory factors are not permanently repressed after embryonic development and that derepression plays a role in the repair of terminally differentiated myofibers.

Role of MyoD in denervated, disused, and exercised muscle

“…qmf1 expression occurred as early as 0.5 h after the onset of stretching. It was six times more abundant than in control muscles of the contralateral side between 3 and 6 h, and then it rapidly downregulated and reached baseline levels by 24 h. qmf1 mRNA was low in control muscle and muscle stretched for 24 -72 h. 36 Constant low levels of MyoD mRNA following an early rapid up-and downregulation in the first 24 h might explain why in the two previously mentioned studies 15,16 no increase in MyoD mRNA per muscle mass could be detected after several days of overloading. In contrast to the chicken, stretch-induced increase in MyoD mRNA levels appears to peak later in rats.…”

“…15,16 Only total MyoD mRNA content per muscle was increased after 3 days (52%), 15 6 days (202%), 15 14 days (149%), 16 and 21 days (57%). 16 In contrast to these two studies, Eppley et al 36 found a pronounced increase in the expression of qmf1, the avian homolog to MyoD, by stretchoverloading the chicken ALD using the same model. qmf1 expression occurred as early as 0.5 h after the onset of stretching.…”

“…38,87 This confirms an attenuation of MyoD expression after experiencing the stretching stimulus for several days, similar to that found in chicken ALD. 15,16,36 By increasing the intensity of the stretch overload, the downregulation of MyoD expression to preintervention levels might be delayed, since after 3 days of passive stretching by cast immobilization of the ankle in a dorsiflexed position, MyoD mRNA and protein content of the rat soleus were increased 5-fold and 165%, respectively. 116 Increasing the mechanical stimulus even more by electrically stimulating the stretched rat tibialis anterior muscle for 1 h caused MyoD expression to progressively rise from days 1 to 7 afterward compared to the untreated contralateral muscle.…”

Temporal expression of regulatory and structural muscle proteins during myogenesis of satellite cells on isolated adult rat fibers

“…Immunocytochemical localization of MyoD and myogenin in mouse following muscle grafting identified the antigens first in mono-nucleated cells (presumably satellite cells) and subsequently in nuclei of regenerating fibers (Füchtbauer and Westphal, 1992). In contrast, mRNA transcript localization in chicken muscle following a brief period of muscle stretch suggested that the MyoD homologue is expressed by nuclei within the fibers (Eppley et al, 1993). Likewise, it was suggested that MyoD and myogenin protein antigens are expressed in myofibers of rat diaphragm following denervation, being first detected about 2.5 days following denervation (Weis, 1994).…”

Stretch-induced myogenin, MyoD, and MRF4 expression and acute hypertrophy in quail slow-tonic muscle are not dependent upon satellite cell proliferation

“…Induction of MRF mRNA has also been reported in fully differentiated myofibers. For example, MRF mRNAs are upregulated in regenerating (Eppley et al 1993;Füchtabauer and Westphal 1992;Grounds et al 1992;Koishi et al 1995) and hypertrophic (Carson and Booth 1998;Jacobs-El et al 1995;Lowe et al 1998) skeletal muscle.…”