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Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy.

Lee YS, Lehar A, Sebald S, Liu M, Swaggart KA, Talbot CC, Pytel P, Barton ER, McNally EM, Lee SJ - Hum. Mol. Genet. (2015)

Bottom Line: As a result, there is extensive effort directed at developing drugs capable of targeting myostatin to treat patients with muscle loss.Despite these potentially beneficial effects, ACVR2B/Fc treatment caused increases in serum CK levels in some Dysf(-/-) mice, indicating possible muscle damage induced by hypertrophy.These findings suggest that depending on the disease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which need to be weighed against the potential gains in muscle growth and decreased fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics and.

No MeSH data available.


Related in: MedlinePlus

Heat maps of enriched top biological processes from GO analysis. (A) Heat map corresponding to response to stress (205 genes). Note that F66 and F66;Dysf−/− are grouped together. (B) Heat map corresponding to inflammatory response (73 genes). Note that ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. (C) Heat map corresponding to response to wounding (73 genes). Note that Dysf−/−, ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. Data represent averages of three independent experiments in red (enriched) or blue (depleted). GO analysis was conducted for significantly differentially expressed genes (fold change >2.0 and P < 0.01), and enriched top biological processes are shown in Supplementary Material, Table S9. List of genes in each biological process with relative expression levels (fold change compared with wt) is shown in Supplementary Material, Dataset.
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DDV288F5: Heat maps of enriched top biological processes from GO analysis. (A) Heat map corresponding to response to stress (205 genes). Note that F66 and F66;Dysf−/− are grouped together. (B) Heat map corresponding to inflammatory response (73 genes). Note that ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. (C) Heat map corresponding to response to wounding (73 genes). Note that Dysf−/−, ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. Data represent averages of three independent experiments in red (enriched) or blue (depleted). GO analysis was conducted for significantly differentially expressed genes (fold change >2.0 and P < 0.01), and enriched top biological processes are shown in Supplementary Material, Table S9. List of genes in each biological process with relative expression levels (fold change compared with wt) is shown in Supplementary Material, Dataset.

Mentions: Biological processes altered by either Fst overexpression or ACVR2B/Fc treatment were detected by Gene ontology (GO) analysis (Supplementary Material, Table S9). The differential expression patterns of genes involved in processes related to response to stress were observed and shown in their heat maps (Fig. 5; for additional details, see Supplementary Material, Dataset). Fst overexpression in both wt and Dysf−/− background dramatically changed the expression pattern of genes related to response to stress (Fig. 5A). Hypertrophy induced by either Fst overexpression or ACVR2B/Fc treatment in Dysf−/− background resulted in similar expression patterns of genes related to inflammatory responses (Fig. 5B) and response to wounding (Fig. 5C), consistent with the important membrane repair function of dysferlin. Hence, the differences that we observed on muscle mass and histopathology among the various experimental groups were clearly reflected in the differential expression patterns of genes related to altered biological processes.Figure 5.


Muscle hypertrophy induced by myostatin inhibition accelerates degeneration in dysferlinopathy.

Lee YS, Lehar A, Sebald S, Liu M, Swaggart KA, Talbot CC, Pytel P, Barton ER, McNally EM, Lee SJ - Hum. Mol. Genet. (2015)

Heat maps of enriched top biological processes from GO analysis. (A) Heat map corresponding to response to stress (205 genes). Note that F66 and F66;Dysf−/− are grouped together. (B) Heat map corresponding to inflammatory response (73 genes). Note that ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. (C) Heat map corresponding to response to wounding (73 genes). Note that Dysf−/−, ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. Data represent averages of three independent experiments in red (enriched) or blue (depleted). GO analysis was conducted for significantly differentially expressed genes (fold change >2.0 and P < 0.01), and enriched top biological processes are shown in Supplementary Material, Table S9. List of genes in each biological process with relative expression levels (fold change compared with wt) is shown in Supplementary Material, Dataset.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581601&req=5

DDV288F5: Heat maps of enriched top biological processes from GO analysis. (A) Heat map corresponding to response to stress (205 genes). Note that F66 and F66;Dysf−/− are grouped together. (B) Heat map corresponding to inflammatory response (73 genes). Note that ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. (C) Heat map corresponding to response to wounding (73 genes). Note that Dysf−/−, ACVR2B/Fc-injected Dysf−/− and F66;Dysf−/− are grouped together. Data represent averages of three independent experiments in red (enriched) or blue (depleted). GO analysis was conducted for significantly differentially expressed genes (fold change >2.0 and P < 0.01), and enriched top biological processes are shown in Supplementary Material, Table S9. List of genes in each biological process with relative expression levels (fold change compared with wt) is shown in Supplementary Material, Dataset.
Mentions: Biological processes altered by either Fst overexpression or ACVR2B/Fc treatment were detected by Gene ontology (GO) analysis (Supplementary Material, Table S9). The differential expression patterns of genes involved in processes related to response to stress were observed and shown in their heat maps (Fig. 5; for additional details, see Supplementary Material, Dataset). Fst overexpression in both wt and Dysf−/− background dramatically changed the expression pattern of genes related to response to stress (Fig. 5A). Hypertrophy induced by either Fst overexpression or ACVR2B/Fc treatment in Dysf−/− background resulted in similar expression patterns of genes related to inflammatory responses (Fig. 5B) and response to wounding (Fig. 5C), consistent with the important membrane repair function of dysferlin. Hence, the differences that we observed on muscle mass and histopathology among the various experimental groups were clearly reflected in the differential expression patterns of genes related to altered biological processes.Figure 5.

Bottom Line: As a result, there is extensive effort directed at developing drugs capable of targeting myostatin to treat patients with muscle loss.Despite these potentially beneficial effects, ACVR2B/Fc treatment caused increases in serum CK levels in some Dysf(-/-) mice, indicating possible muscle damage induced by hypertrophy.These findings suggest that depending on the disease context, inducing muscle hypertrophy by myostatin blockade may have detrimental effects, which need to be weighed against the potential gains in muscle growth and decreased fibrosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology and Genetics and.

No MeSH data available.


Related in: MedlinePlus