Transcriptome analysis of collagen VI-related muscular dystrophy muscle biopsies.
Ann Clin Transl Neurol
; 8(11): 2184-2198, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-34729958
ABSTRACT
OBJECTIVE:
To define the transcriptomic changes responsible for the histologic alterations in skeletal muscle and their progression in collagen VI-related muscular dystrophy (COL6-RD).METHODS:
COL6-RD patient muscle biopsies were stratified into three groups based on the overall level of pathologic severity considering degrees of fibrosis, muscle fiber atrophy, and fatty replacement of muscle tissue. Using microarray and RNA-Seq, we then performed global gene expression profiling on the same muscle biopsies and compared their transcriptome with age- and sex-matched controls.RESULTS:
COL6-RD muscle biopsy transcriptomes as a group revealed prominent upregulation of muscle extracellular matrix component genes and the downregulation of skeletal muscle and mitochondrion-specific genes. Upregulation of the TGFß pathway was the most conspicuous change across all biopsies and was fully evident even in the mildest/earliest histological group. There was no difference in the overall transcriptional signature between the different histologic groups but polyserial analysis identified relative changes along with COL6-RD histological severity.INTERPRETATION:
Overall, our study establishes the prominent dysregulation of extracellular matrix genes, TGFß signaling, and its downstream cellular pathways at the transcriptomic level in COL6-RD muscle.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator de Crescimento Transformador beta
/
Perfilação da Expressão Gênica
/
Colágeno Tipo VI
/
Matriz Extracelular
/
Distrofias Musculares
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article