Dataset Information

Reduced prostaglandin I₂ signaling in Arid5b^-/- primary skeletal muscle cells attenuates myogenesis.

ABSTRACT: The AT-rich interaction domain (ARID) family of proteins regulates gene expression, development, and differentiation. Although Arid5b has important functions in adipogenesis and chondrogenesis, the role of Arid5b in skeletal muscle myogenesis has not been investigated. Therefore, we isolated primary skeletal muscle cells from Arid5b^+/+ and Arid5b^-/- mice and characterized differentiation in these cells. We found that Arid5b^-/- primary skeletal muscle cells showed differentiation defects and impaired sarcomeric assembly. Microarray analysis revealed down-regulation of the prostanoid biosynthesis pathway in Arid5b^-/- myoblasts, including the genes encoding cyclooxygenase (COX)-1 ( Ptgs1) and prostaglandin (PG)I synthase ( Ptgis). Down-regulation of COX-1 and PGI synthase was confirmed by real-time PCR and Western blot analyses. Correspondingly, the production of PGI₂, as measured by ELISA, was reduced in Arid5b^-/- cells relative to Arid5b^+/+ cells. Boyden chamber assays showed that migration was increased but chemotaxis was impaired in Arid5b^-/- cells. Myoblast fusion was also inhibited in Arid5b^-/- cells compared with Arid5b^+/+ cells. Treatment with the PGI₂ analog iloprost rescued the defects in myotube formation, migration, and fusion. These results demonstrate that Arid5b has a novel and essential role in skeletal muscle differentiation by regulating PGI₂ production.-Murray, J., Whitson, R. H., Itakura, K. Reduced prostaglandin I₂ signaling in Arid5b^-/- primary skeletal muscle cells attenuates myogenesis.

SUBMITTER: Murray J

PROVIDER: S-EPMC5893174 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Reduced prostaglandin I2 signaling in Arid5b-/- primary skeletal muscle cells attenuates myogenesis.

Murray Jennifer J Whitson Robert H RH Itakura Keiichi K

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20180105 4

The AT-rich interaction domain (ARID) family of proteins regulates gene expression, development, and differentiation. Although Arid5b has important functions in adipogenesis and chondrogenesis, the role of Arid5b in skeletal muscle myogenesis has not been investigated. Therefore, we isolated primary skeletal muscle cells from Arid5b+/+ and Arid5b-/- mice and characterized differentiation in these cells. We found that Arid5b-/- primary skeletal muscle cells showed ...[more]

PMID: 29196500

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Project description:Myotonic dystrophy type 1 (DM1) and 2 (DM2) are autosomal dominant degenerative neuromuscular disorders characterized by progressive skeletal muscle weakness, atrophy, and myotonia with progeroid features. Although both DM1 and DM2 are characterized by skeletal muscle dysfunction and also share other clinical features, the diseases differ in the muscle groups that are affected. In DM1, distal muscles are mainly affected, whereas in DM2 problems are mostly found in proximal muscles. In addition, manifestation in DM1 is generally more severe, with possible congenital or childhood-onset of disease and prominent CNS involvement. DM1 and DM2 are caused by expansion of (CTG•CAG)n and (CCTG•CAGG)n repeats in the 3' non-coding region of DMPK and in intron 1 of CNBP, respectively, and in overlapping antisense genes. This critical review will focus on the pleiotropic problems that occur during development, growth, regeneration, and aging of skeletal muscle in patients who inherited these expansions. The current best-accepted idea is that most muscle symptoms can be explained by pathomechanistic effects of repeat expansion on RNA-mediated pathways. However, aberrations in DNA replication and transcription of the DM loci or in protein translation and proteome homeostasis could also affect the control of proliferation and differentiation of muscle progenitor cells or the maintenance and physiological integrity of muscle fibers during a patient's lifetime. Here, we will discuss these molecular and cellular processes and summarize current knowledge about the role of embryonic and adult muscle-resident stem cells in growth, homeostasis, regeneration, and premature aging of healthy and diseased muscle tissue. Of particular interest is that also progenitor cells from extramuscular sources, such as pericytes and mesoangioblasts, can participate in myogenic differentiation. We will examine the potential of all these types of cells in the application of regenerative medicine for muscular dystrophies and evaluate new possibilities for their use in future therapy of DM.

Project description:BackgroundAcute injury to skeletal muscle damages myofibers and fragment capillaries, impairing contractile function and local perfusion. Myofibers and microvessels regenerate from satellite cells and from surviving microvessel fragments, respectively, to restore intact muscle. Established models of injury have used myotoxins and physical trauma to demonstrate the concurrence of myogenesis and angiogenesis during regeneration. In these models, efferocytosis removes cellular debris while basal laminae persist to provide guidance during myofiber and microvessel regeneration. It is unknown whether the spatiotemporal coupling between myofiber and microvascular regeneration persists when muscle tissue is completely removed and local guidance cues are lost.MethodsTo test whether complete removal of skeletal muscle tissue affects the spatiotemporal relationship between myogenesis and angiogenesis during regeneration, subthreshold volumetric muscle loss was created with a biopsy punch (diameter, 2 mm) through the center of the gluteus maximus (GM) in adult mice. Regeneration into the void was evaluated through 21 days post-injury (dpi). Microvascular perfusion was evaluated in vivo by injecting fluorescent dextran into the circulation during intravital imaging. Confocal imaging and histological analyses of whole-mount GM preparations and tissue cross-sections assessed the growth of microvessels and myofibers into the wound.ResultsA provisional matrix filled with PDGFRα+ and CD45+ cells spanned the wound within 1 dpi. Regenerating microvessels advanced from the edges of the wound into the matrix by 7 dpi. Nascent microvascular networks formed by 10 dpi with blood-perfused networks spanning the wound by 14 dpi. In striking contrast, the wound remained devoid of myofibers at 7 and 10 dpi. Myogenesis into the wound was apparent by 14 dpi and traversed the wound by 21 dpi. Regenerated myofibers and microvessels were disorganized compared to the uninjured muscle.ConclusionsFollowing punch biopsy of adult skeletal muscle, regenerating microvessels span the wound and become perfused with blood prior to myofiber regeneration. The loss of residual guidance cues with complete tissue removal disrupts the spatiotemporal correspondence between microvascular and myofiber regeneration. We conclude that angiogenesis precedes myogenesis during regeneration following subthreshold volumetric muscle loss.

Dataset Information

Reduced prostaglandin I₂ signaling in Arid5b^-/- primary skeletal muscle cells attenuates myogenesis.

Publications

Reduced prostaglandin I<sub>2</sub> signaling in Arid5b<sup>-/-</sup> primary skeletal muscle cells attenuates myogenesis.

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