PTEN ja SPRY-1 Duchennen lihasdystrofiassa kohdegeenejä.

https://www.ncbi.nlm.nih.gov/pubmed/25892183

Biochim Biophys Acta. 2015 Jul;1852(7):1451-64. doi: 10.1016/j.bbadis.2015.04.013. Epub 2015 Apr 17.

Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy.

Zanotti S¹, Gibertini S¹, Curcio M¹, Savadori P¹, Pasanisi B¹, Morandi L¹, Cornelio F¹, Mantegazza R¹, Mora M².

Abstract

Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition.

Copyright © 2015. Published by Elsevier B.V.

KEYWORDS:

Duchenne muscular dystrophy; Fibroblast; Fibrosis; MiR-21; MiR-29; Myoblast; mdx mouse

PMID:

25892183

DOI:

10.1016/j.bbadis.2015.04.013

[Indexed for MEDLINE]

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• Highlights

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  MiR-21 is increased in DMD patient muscle and fibroblasts and its target genes PTEN and SPRY-1 are reduced.

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  MiR-21 silencing in DMD fibroblasts and mdx mice restores PTEN and SPRY-1 levels.

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  MiR-29a and miR-29c are reduced in DMD muscle and myoblasts.

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  MiR-29 mimicking in DMD myoblasts significantly decreases miR-29 target genes.

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  MiR-21 and miR-29 play opposing roles in muscl
  
  

  GeneCards Summary for SPRY1 Gene

  SPRY1 (Sprouty RTK Signaling Antagonist 1) is a Protein Coding gene. Diseases associated with SPRY1 include Adrenal Cortical Adenocarcinoma and Legius Syndrome. Among its related pathways are Signaling by GPCR and Angiogenesis (CST). An important paralog of this gene is SPRY2.