Possible role for the c‐ski gene in the proliferation of myogenic cells in regenerating skeletal muscles of rats

Abstract

Skeletal muscle regeneration after injury involves various processes, such as infiltration by inflammatory cells, the proliferation of satellite cells and fusion to myotubes. The c-ski nuclear protein has been implicated in the control of cell proliferation and/or terminal differentiation in the growth of skeletal muscle. However, there have been no reports concerning the involution of c-ski in the regeneration of injured skeletal muscle in mammals. A possible role for c-ski in the proliferation of myogenic cells in rat skeletal muscle during regeneration has been investigated with the assistance of in vitro experiments with L6 skeletal muscle cells. The expression levels of c-ski mRNA in regenerating tissues increased to approximately threefold that of intact tissues at 2 days after injury and decreased to normal levels at 2 weeks after injury. Many mononuclear cells among the Ski-positive cells expressed desmin and proliferating cell nuclear antigen, indicating that Ski-producing cells include the proliferating myogenic cells. The proliferation of L6 cells was significantly retarded by expression of the antisense ski gene. The results of the present study reveal that the c-ski gene plays an important role in the proliferation of myogenic cells in the regeneration of injured skeletal muscle.

Key signalling factors and pathways in the molecular determination of skeletal muscle phenotype

“…Therefore, a mechanism of the transforming ability of Ski (and SnoN) is the repression of Smad function, whose inactivation prevents TGF-b-induced cell cycle arrest. The up-regulation of Ski in proliferating satellite cells points to its possible role in mediating cell proliferation in the regeneration of damaged fibres (Soeta et al, 2001). The mechanisms behind the effects of Ski on muscle differentiation and hypertrophy are unknown.…”

Expression of Ski in the Granulosa Cells of Atretic Follicles in the Rat Ovary

“…For example, Ski is expressed in proliferating myoblast [6] and uterine epithelial cells [7]. In the uterus, endometrial c-ski gene expression has been induced by estrogen treatment, which is known to induce proliferation of uterine epithelial cells [7], and progesterone treatment eliminated estrogeninduced c-ski expression [30].…”

“…Transgenic mice expressing the c-ski gene under the control of a murine sarcoma virus long terminal repeat show large increases in their skeletal muscle mass [2], while c-ski-deficient mice have defects in their skeletal muscle development [3]. In addition, mice lacking c-ski show perinatal lethality due to defects in neurulation and craniofacial patterning as well as skeletal muscle development, and excessive apoptosis has been detected in c-skideficient mouse embryos [4,5], supporting the idea that Ski can act as an anti-apoptotic factor [6]. It has also been suggested that c-ski is involved in mediating the proliferative effect of 17β-estradiol in uterine epithelial cells [7].…”

“…2, the granulosa cells of follicles exhibited both positive and negative staining for Ski regardless of the size of follicles. Since Ski has been implicated as playing roles in cell proliferation [4,6,7] and has been predicted to act as an anti-apoptotic factor [5], the above results showing a distinct Ski protein expression pattern in granulosa cells led us to examine the relationship (Fig. 3D-F).…”

Células satélites musculares

“…Durante a regeneração muscular, ocorre aumento na expressão da c-ski, sendo muitas células também positivas para PCNA e desmina (26) . 2o) p27 kip -há uma relação inversa entre a capacidade proliferativa da CS e a abundância da proteína p27 Kip, podendo estar envolvida no crescimento e na hipertrofia musculares (27) .…”