Dataset Information

Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions.

ABSTRACT: Skeletal muscle holds an intrinsic capability of growth and regeneration both in physiological conditions and in case of injury. Chronic muscle illnesses, generally caused by genetic and acquired factors, lead to deconditioning of the skeletal muscle structure and function, and are associated with a significant loss in muscle mass. At the same time, progressive muscle wasting is a hallmark of aging. Given the paracrine properties of myogenic stem cells, extracellular vesicle-derived signals have been studied for their potential implication in both the pathogenesis of degenerative neuromuscular diseases and as a possible therapeutic target. In this study, we screened the content of extracellular vesicles from animal models of muscle hypertrophy and muscle wasting associated with chronic disease and aging. Analysis of the transcriptome, protein cargo and microRNAs (miRNAs) allowed us to identify a hypertrophic miRNA signature amenable for targeting muscle wasting, consisting of miR-1 and miR-208a. We tested this signature among others in vitro on mesoangioblasts (MABs), vessel-associated adult stem cells, and we observed an increase in the efficiency of myogenic differentiation. Furthermore, injections of miRNA-treated MABs in aged mice resulted in an improvement in skeletal muscle features, such as muscle weight, strength and cross-sectional area compared to controls. Overall, we provide evidence that the extracellular vesicle-derived miRNA signature we identified enhances the myogenic potential of myogenic stem cells.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Rita Derua

LAB HEAD: Prof. Maurilio Sampaolesi

PROVIDER: PXD035446 | Pride | 2022-11-09

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	2018 10_20_38 PM;File Size_ 466704671 [Byte] (F034881).mzid.gz	Mzid
	2018 10_20_38 PM;File Size_ 466704671 [Byte] (F034881).mzid_2018_10_20_38_PM_File_Size__466704671__Byte__(F034881).MGF	Mzid
	2018 11_39_54 AM;File Size_ 460803183 [Byte] (F034879).mzid.gz	Mzid
	2018 11_39_54 AM;File Size_ 460803183 [Byte] (F034879).mzid_2018_11_39_54_AM_File_Size__460803183__Byte__(F034879).MGF	Mzid
	2018 12_23_32 AM;File Size_ 480777990 [Byte] (F034872).mzid.gz	Mzid

Items per page:

1 - 5 of 37

Similar Datasets

Project description:Protein-leucine supplement ingestion following strenuous endurance exercise accentuates skeletal-muscle protein synthesis and adaptive molecular responses, but the underlying transcriptome is uncharacterized. In a randomized single-blind triple-crossover design, 12 trained men completed 100 min of high-intensity cycling then ingested either 70/15/180/30g protein/leucine/carbohydrate/fat (15LEU), 23/5/180/30g (5LEU) or 0/0/274/30g (CON) beverages during the first 90 min of a 240-min recovery period. Vastus lateralis muscle samples (30 and 240-min post-exercise) underwent transcriptome analysis by microarray followed by bioinformatic analysis. Gene expression was regulated by Protein-leucine in a dose-dependent manner impacting the inflammatory response, muscle growth and development. At 30 min, 15LEU and 5LEU vs. CON activated transcriptome networks with geneset functions involving cell-cycle arrest (Z-score 2.0-2.7; P<0.01), leukocyte maturation (1.7; P=0.007), cell viability (2.4; P=0.005), promyogenic networks encompassing myocyte differentiation and myogenin (MYOD1, MYOG), and a proteinaceous extracellular matrix, adhesion, and development programme correlated with plasma lysine, arginine, tyrosine, taurine, glutamic acid, and asparagine concentrations. High protein-leucine dose (15LEU-5LEU) activated an IL1b-centered proinflammatory network and leukocyte migration, differentiation, and survival functions (2.0-2.6; <0.001). By 240 min, the protein-leucine transcriptome was anti-inflammatory and promyogenic (IL-6, NF-kÎ², SMAD, STAT3 network inhibition), with overrepresented functions including decreased leukocyte migration and connective tissue development (-1.8-2.4; P<0.01), increased apoptosis of myeloid and muscle cells (2.2-3.0; P<0.002) and cell metabolism (2.0-2.4; P<0.01). The analysis suggests protein-leucine ingestion modulates inflammatory-myogenic regenerative processes during skeletal muscle recovery from endurance exercise. Further cellular and translational research is warranted to validate amino acid-mediated myeloid and myocellular mechanisms within skeletal-muscle functional plasticity. Total RNA obtained from isolated skeletal muscles

Dataset Information

Extracellular vesicle-derived miRNAs improve stem cell-based therapeutic approaches in muscle wasting conditions.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets