Dataset Information

The clearance of cell remnants and the regeneration of the injured muscle depend on soluble pattern recognition receptor PTX3.

ABSTRACT:

Objective

The signals causing the resolution of muscle inflammation are only partially characterized. The long pentraxin PTX3, which modulates leukocyte recruitment and activation, could contribute.

Methods

We analysed the expression of ptx3 after muscle injury and verified whether hematopoietic precursors are a source of the protein. The kinetics of regeneration and leukocytes infiltration, the accumulation of cell remnants and anti-histidyl-t-RNA synthetase autoantibodies were compared in wild-type and ptx3-deficient mice.

Results

Ptx3 expression was up-regulated three-five days after injury and restricted to the extracellular matrix. Cellular debris and leukocytes persisted in the muscle of ptx3-deficient mice for a long time after wild-type animals had healed. ptx3-deficient macrophages expressed receptors involved in apoptotic cell clearance and engulfed dead cells in vitro. Accumulation of cell debris in a pro-inflammatory microenvironment was not sufficient to elicit autoantibodies.

Conclusion

PTX3 generated in response to muscle injury prompts the clearance of debris and the termination of the inflammatory response.

SUBMITTER: Vezzoli M

PROVIDER: S-EPMC5263058 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

The clearance of cell remnants and the regeneration of the injured muscle depend on soluble pattern recognition receptor PTX3.

Vezzoli Michela M Sciorati Clara C Campana Lara L Monno Antonella A Doglio Maria Giulia MG Rigamonti Elena E Corna Gianfranca G Touvier Thierry T Castiglioni Alessandra A Capobianco Annalisa A Mantovani Alberto A Manfredi Angelo A AA Garlanda Cecilia C Rovere-Querini Patrizia P

Molecular medicine (Cambridge, Mass.) 20161123

<h4>Objective</h4>The signals causing the resolution of muscle inflammation are only partially characterized. The long pentraxin PTX3, which modulates leukocyte recruitment and activation, could contribute.<h4>Methods</h4>We analysed the expression of ptx3 after muscle injury and verified whether hematopoietic precursors are a source of the protein. The kinetics of regeneration and leukocytes infiltration, the accumulation of cell remnants and anti-histidyl-t-RNA synthetase autoantibodies were c ...[more]

PMID: 27900389

Similar Datasets

Project description:BackgroundPresently, there is no effective treatment for the lethal muscle wasting disease Duchenne muscular dystrophy (DMD). Here we show that increased sphingosine-1-phoshate (S1P) through direct injection or via the administration of the small molecule 2-acetyl-4(5)-tetrahydroxybutyl imidazole (THI), an S1P lyase inhibitor, has beneficial effects in acutely injured dystrophic muscles of mdx mice.MethodsWe treated mdx mice with and without acute injury and characterized the histopathological and functional effects of increasing S1P levels. We also tested exogenous and direct administration of S1P on mdx muscles to examine the molecular pathways under which S1P promotes regeneration in dystrophic muscles.ResultsShort-term treatment with THI significantly increased muscle fiber size and extensor digitorum longus (EDL) muscle specific force in acutely injured mdx limb muscles. In addition, the accumulation of fibrosis and fat deposition, hallmarks of DMD pathology and impaired muscle regeneration, were lower in the injured muscles of THI-treated mdx mice. Furthermore, increased muscle force was observed in uninjured EDL muscles with a longer-term treatment of THI. Such regenerative effects were linked to the response of myogenic cells, since intramuscular injection of S1P increased the number of Myf5nlacz/+ positive myogenic cells and newly regenerated myofibers in injured mdx muscles. Intramuscular injection of biotinylated-S1P localized to muscle fibers, including newly regenerated fibers, which also stained positive for S1P receptor 1 (S1PR1). Importantly, plasma membrane and perinuclear localization of phosphorylated S1PR1 was observed in regenerating muscle fibers of mdx muscles. Intramuscular increases of S1P levels, S1PR1 and phosphorylated ribosomal protein S6 (P-rpS6), and elevated EDL muscle specific force, suggest S1P promoted the upregulation of anabolic pathways that mediate skeletal muscle mass and function.ConclusionsThese data show that S1P is beneficial for muscle regeneration and functional gain in dystrophic mice, and that THI, or other pharmacological agents that raise S1P levels systemically, may be developed into an effective treatment for improving muscle function and reducing the pathology of DMD.

Dataset Information

The clearance of cell remnants and the regeneration of the injured muscle depend on soluble pattern recognition receptor PTX3.

Objective

Methods

Results

Conclusion

Publications

The clearance of cell remnants and the regeneration of the injured muscle depend on soluble pattern recognition receptor PTX3.

Similar Datasets

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