Abstract
The expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to define the role of Trim33 in muscle development and regeneration. We generated mice with muscle-specific conditional knockout of Trim33 by combining floxed Trim33 and Cre recombinase under the Pax7 promoter. Muscle regeneration was induced by injuring mouse muscles with cardiotoxin. We studied the consequences of Trim33 knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. We also studied the effect of Trim33 silencing in satellite cells and the C2C12 mouse muscle cell line. Although Trim33 knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Unexpectedly, RNAseq analysis revealed dramatically increased expression of cholecystokinin (CCK) in regenerating muscle from Trim33 knockout mice, satellite cells from Trim33 knockout mice, and C2C12 cells treated with Trim33 siRNA. Trim33 knockdown had no demonstrable effect on muscle differentiation or regeneration. However, Trim33 knockdown induced CCK expression in muscle, suggesting that suppression of CCK expression requires Trim33.
Highlights
The expression of Trim[33] (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation
We have previously shown that Trim[33] is upregulated in regenerating skeletal muscle fibers of mice following muscle injury[7]
We sought to study its functional role in skeletal muscle in vivo via a conditional knockout mouse, ex vivo using satellite cells, and in vitro using siRNA in C2C12 cells
Summary
The expression of Trim[33] (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Trim[33] is required for the normal development of other tissues, its role in skeletal muscle is unknown. We studied the consequences of Trim[33] knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. Trim[33] knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Trim[33] has been shown to recognize histone modifications indicating poised chromatin, an unmodified H4, H3K9me[3], H3K18ac[2]. It has been implicated in regulating the TGFβ pathway, though this role is not completely understood. We have previously shown that Trim[33] is upregulated in regenerating skeletal muscle fibers of mice following muscle injury[7]. We sought to study its functional role in skeletal muscle in vivo via a conditional knockout mouse, ex vivo using satellite cells, and in vitro using siRNA in C2C12 cells
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