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Mest but Not MiR-335 Affects Skeletal Muscle Growth and Regeneration.

Hiramuki Y, Sato T, Furuta Y, Surani MA, Sehara-Fujisawa A - PLoS ONE (2015)

Bottom Line: When skeletal muscle fibers are injured, they regenerate and grow until their sizes are adjusted to surrounding muscle fibers and other relevant organs.In addition to reduced body weight in Mest+/-; DMD- mice, decreased muscle growth was observed in Mest+/- mice during cardiotoxin-induced regeneration, suggesting roles of Mest in muscle regeneration.Thus, Mest likely mediates muscle regeneration through regulation of imprinted gene networks in skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.

ABSTRACT
When skeletal muscle fibers are injured, they regenerate and grow until their sizes are adjusted to surrounding muscle fibers and other relevant organs. In this study, we examined whether Mest, one of paternally expressed imprinted genes that regulates body size during development, and miR-335 located in the second intron of the Mest gene play roles in muscle regeneration. We generated miR-335-deficient mice, and found that miR-335 is a paternally expressed imprinted microRNA. Although both Mest and miR-335 are highly expressed during muscle development and regeneration, only Mest+/- (maternal/paternal) mice show retardation of body growth. In addition to reduced body weight in Mest+/-; DMD- mice, decreased muscle growth was observed in Mest+/- mice during cardiotoxin-induced regeneration, suggesting roles of Mest in muscle regeneration. Moreover, expressions of H19 and Igf2r, maternally expressed imprinted genes were affected in tibialis anterior muscle of Mest+/-; DMD- mice compared to DMD- mice. Thus, Mest likely mediates muscle regeneration through regulation of imprinted gene networks in skeletal muscle.

No MeSH data available.


Related in: MedlinePlus

Mest is required for body and skeletal muscle growth.(A) Representative images of 4 weeks old mice in individual genotypes. (B and C) Body weights of male littermate WT (n = 3–22), Mest+/- (n = 6–15), DMD- (n = 4–25), and Mest+/-; DMD- mice (n = 4–22) from 1 to 12 (11–13) weeks old. (D) Body weights of WT (n = 15) and miR-335+/Neo (n = 12) mice at 6 weeks. (E) Body weights of WT (n = 8–15) and miR-335+/- mice (n = 15–18) from 1 to 6 weeks old. (F) TA muscle weights of male littermate WT (n = 13), Mest+/- (n = 6), DMD- (n = 18), and Mest+/-; DMD- mice (n = 11) at 6 weeks old. (G) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 6 weeks old. (H) TA muscle weights of male littermate WT (n = 3), Mest+/- (n = 6), DMD- (n = 4), and Mest+/-; DMD- mice (n = 4) at 11–13 weeks old. (I) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 11–13 weeks old. (J and K) The numbers and average cross section areas of TA muscle fibers of male littermate WT (n = 7) and Mest+/- mice (n = 4) at 6 weeks. Error bars indicate the s.e.m. *P < 0.05, ***P < 0.001. NS = Not significant.
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pone.0130436.g003: Mest is required for body and skeletal muscle growth.(A) Representative images of 4 weeks old mice in individual genotypes. (B and C) Body weights of male littermate WT (n = 3–22), Mest+/- (n = 6–15), DMD- (n = 4–25), and Mest+/-; DMD- mice (n = 4–22) from 1 to 12 (11–13) weeks old. (D) Body weights of WT (n = 15) and miR-335+/Neo (n = 12) mice at 6 weeks. (E) Body weights of WT (n = 8–15) and miR-335+/- mice (n = 15–18) from 1 to 6 weeks old. (F) TA muscle weights of male littermate WT (n = 13), Mest+/- (n = 6), DMD- (n = 18), and Mest+/-; DMD- mice (n = 11) at 6 weeks old. (G) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 6 weeks old. (H) TA muscle weights of male littermate WT (n = 3), Mest+/- (n = 6), DMD- (n = 4), and Mest+/-; DMD- mice (n = 4) at 11–13 weeks old. (I) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 11–13 weeks old. (J and K) The numbers and average cross section areas of TA muscle fibers of male littermate WT (n = 7) and Mest+/- mice (n = 4) at 6 weeks. Error bars indicate the s.e.m. *P < 0.05, ***P < 0.001. NS = Not significant.

Mentions: Mest+/- mice show growth retardation ([2], Fig 3A and 3B). miR-335+/Neo mice, in contrast, did not show a reduction in body weight compared to WT mice significantly (Fig 3D). miR-335+/- mice exhibited mild growth defects (Fig 3E), which is likely due to decreased expression of Mest in miR-335+/- mice (Fig 2H). Based on these results, we concluded that Mest, but not miR-335, is involved in regulation of body size during development. When TA muscles of WT and Mest+/- mice were compared at 6 and 11–13 weeks of age, those of the latter were significantly smaller than those of the former (Fig 3F and 3H). Moreover, numbers of muscle fibers are significantly less in Mest+/- mice (Fig 3J). In contrast, the ratio of TA weight/Body weight and the average cross section areas of TA muscles of both WT and Mest+/- mice were similar to each other (Fig 3G, 3I and 3K).


Mest but Not MiR-335 Affects Skeletal Muscle Growth and Regeneration.

Hiramuki Y, Sato T, Furuta Y, Surani MA, Sehara-Fujisawa A - PLoS ONE (2015)

Mest is required for body and skeletal muscle growth.(A) Representative images of 4 weeks old mice in individual genotypes. (B and C) Body weights of male littermate WT (n = 3–22), Mest+/- (n = 6–15), DMD- (n = 4–25), and Mest+/-; DMD- mice (n = 4–22) from 1 to 12 (11–13) weeks old. (D) Body weights of WT (n = 15) and miR-335+/Neo (n = 12) mice at 6 weeks. (E) Body weights of WT (n = 8–15) and miR-335+/- mice (n = 15–18) from 1 to 6 weeks old. (F) TA muscle weights of male littermate WT (n = 13), Mest+/- (n = 6), DMD- (n = 18), and Mest+/-; DMD- mice (n = 11) at 6 weeks old. (G) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 6 weeks old. (H) TA muscle weights of male littermate WT (n = 3), Mest+/- (n = 6), DMD- (n = 4), and Mest+/-; DMD- mice (n = 4) at 11–13 weeks old. (I) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 11–13 weeks old. (J and K) The numbers and average cross section areas of TA muscle fibers of male littermate WT (n = 7) and Mest+/- mice (n = 4) at 6 weeks. Error bars indicate the s.e.m. *P < 0.05, ***P < 0.001. NS = Not significant.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4476715&req=5

pone.0130436.g003: Mest is required for body and skeletal muscle growth.(A) Representative images of 4 weeks old mice in individual genotypes. (B and C) Body weights of male littermate WT (n = 3–22), Mest+/- (n = 6–15), DMD- (n = 4–25), and Mest+/-; DMD- mice (n = 4–22) from 1 to 12 (11–13) weeks old. (D) Body weights of WT (n = 15) and miR-335+/Neo (n = 12) mice at 6 weeks. (E) Body weights of WT (n = 8–15) and miR-335+/- mice (n = 15–18) from 1 to 6 weeks old. (F) TA muscle weights of male littermate WT (n = 13), Mest+/- (n = 6), DMD- (n = 18), and Mest+/-; DMD- mice (n = 11) at 6 weeks old. (G) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 6 weeks old. (H) TA muscle weights of male littermate WT (n = 3), Mest+/- (n = 6), DMD- (n = 4), and Mest+/-; DMD- mice (n = 4) at 11–13 weeks old. (I) TA/Body weights of male littermate WT, Mest+/-, DMD-, and Mest+/-; DMD- mice at 11–13 weeks old. (J and K) The numbers and average cross section areas of TA muscle fibers of male littermate WT (n = 7) and Mest+/- mice (n = 4) at 6 weeks. Error bars indicate the s.e.m. *P < 0.05, ***P < 0.001. NS = Not significant.
Mentions: Mest+/- mice show growth retardation ([2], Fig 3A and 3B). miR-335+/Neo mice, in contrast, did not show a reduction in body weight compared to WT mice significantly (Fig 3D). miR-335+/- mice exhibited mild growth defects (Fig 3E), which is likely due to decreased expression of Mest in miR-335+/- mice (Fig 2H). Based on these results, we concluded that Mest, but not miR-335, is involved in regulation of body size during development. When TA muscles of WT and Mest+/- mice were compared at 6 and 11–13 weeks of age, those of the latter were significantly smaller than those of the former (Fig 3F and 3H). Moreover, numbers of muscle fibers are significantly less in Mest+/- mice (Fig 3J). In contrast, the ratio of TA weight/Body weight and the average cross section areas of TA muscles of both WT and Mest+/- mice were similar to each other (Fig 3G, 3I and 3K).

Bottom Line: When skeletal muscle fibers are injured, they regenerate and grow until their sizes are adjusted to surrounding muscle fibers and other relevant organs.In addition to reduced body weight in Mest+/-; DMD- mice, decreased muscle growth was observed in Mest+/- mice during cardiotoxin-induced regeneration, suggesting roles of Mest in muscle regeneration.Thus, Mest likely mediates muscle regeneration through regulation of imprinted gene networks in skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.

ABSTRACT
When skeletal muscle fibers are injured, they regenerate and grow until their sizes are adjusted to surrounding muscle fibers and other relevant organs. In this study, we examined whether Mest, one of paternally expressed imprinted genes that regulates body size during development, and miR-335 located in the second intron of the Mest gene play roles in muscle regeneration. We generated miR-335-deficient mice, and found that miR-335 is a paternally expressed imprinted microRNA. Although both Mest and miR-335 are highly expressed during muscle development and regeneration, only Mest+/- (maternal/paternal) mice show retardation of body growth. In addition to reduced body weight in Mest+/-; DMD- mice, decreased muscle growth was observed in Mest+/- mice during cardiotoxin-induced regeneration, suggesting roles of Mest in muscle regeneration. Moreover, expressions of H19 and Igf2r, maternally expressed imprinted genes were affected in tibialis anterior muscle of Mest+/-; DMD- mice compared to DMD- mice. Thus, Mest likely mediates muscle regeneration through regulation of imprinted gene networks in skeletal muscle.

No MeSH data available.


Related in: MedlinePlus