Objective: 

The serum- and glucocorticoid-inducible kinase SGK1 contributes to a variety of physiological functions, such as regulation of gene expression, metabolism and membrane transport. Under certain pathophysiological conditions SGK1 can stimulate fibrosis and thereby aggravate dysfunction and failure of organs. In this study we investigated whether lack of SGK1 influences structure, function and/or fibrosis development of dystrophin-deficient mdx muscle.

Methods: 

Force measurements were performed on isolated soleus muscles and diaphragm segments from 100 d old mdx and wildtype mice, SGK1 deficient (sgk1^-/-) mice, and on muscles of a newly bred mdx mutant, lacking both, dystrophin and SGK1 (mdx/sgk1^-/-). Histological analyses of several hindlimb muscles and diaphragm included H&E staining of cryosections to quantify central nuclei in muscle fibers. Sirius red staining was applied to quantify connective tissue.

Results: 

Mdx muscles showed the typical pathological features of muscular dystrophy. Specific force was reduced (on average by 30% for soleus muscles and by 50% for diaphragm segments; n=7/7). In addition muscle fatigue occurred faster in mdx muscles. Most mdx muscle fibers contained central nuclei. The area covered by connective tissue in muscle cross sections was increased (on average 7% in mdx vs. 3.5% in wildtype muscles). The histological appearance of muscles from sgk1-/- mice was overall intact. Central nuclei were not observed and the fraction of connective tissue was identical to that of wildtype muscle. However, specific force was significantly reduced in SGK1-deficient muscles (force reduction: 20% for soleus muscles and 25% for diaphragm segments, n=7/7). Surprisingly, mdx/sgk1^-/- mice did not display significantly reduced force of soleus muscles and only a slight force reduction of the diaphragm segments (by 20%, n=7/7). Most muscle fibers of the double mutants contained central nuclei, but fibrosis was not observed. The area covered by connective tissue was not higher than that in the wildtype mice.

Conclusion: 

The sole lack of SGK1 in mouse muscle does not lead to pronounced changes in muscle structure and function. However, dystrophin-deficient mdx muscle seems to benefit form SGK1 deficiency. SGK1 appears to be an important player in the process of fibrotic remodeling and subsequent weakness of dystrophin-deficient mouse muscle.