Hippo signaling pathway is altered in Duchenne muscular dystrophy
| Autor: | M'hammed Aguennouz, Anna Ciranni, Sonia Messina, Francesca Polito, Gian Luca Vita, Roberto Arrigo, Olimpia Musumeci, Rosa Maria Di Giorgio, Giuseppe Vita, Rosaria Oteri, Carmelo Rodolico |
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| Rok vydání: | 2018 |
| Předmět: |
Genetics and Molecular Biology (all)
0301 basic medicine Myoblast proliferation Heredity Genetic Linkage Survivin Duchenne muscular dystrophy Muscle Proteins lcsh:Medicine Cell Cycle Proteins Duchenne Muscular Dystrophy Biochemistry Muscular Dystrophies Biochemistry Genetics and Molecular Biology (all) Agricultural and Biological Sciences (all) Medicine and Health Sciences Morphogenesis Post-Translational Modification Phosphorylation Muscular dystrophy Child lcsh:Science Musculoskeletal System Tissue homeostasis YAP1 Multidisciplinary Muscles Middle Aged Muscle Differentiation Cell biology Nucleic acids Neurology X-Linked Traits Sex Linkage Child Preschool Anatomy Signal transduction Muscle Regeneration Signal Transduction Research Article Adult Adolescent Mice Transgenic Protein Serine-Threonine Kinases Biology Young Adult 03 medical and health sciences Genetics medicine Animals Humans Regeneration RNA Messenger Kinase activity Muscle Skeletal Non-coding RNA Adaptor Proteins Signal Transducing Clinical Genetics Natural antisense transcripts Hippo signaling pathway lcsh:R Biology and Life Sciences Proteins YAP-Signaling Proteins Phosphoproteins medicine.disease Gene regulation Mice Inbred C57BL Muscular Dystrophy Duchenne MicroRNAs 030104 developmental biology Muscular Dystrophies Limb-Girdle Skeletal Muscles RNA lcsh:Q Gene expression Organism Development Transcription Factors Developmental Biology |
| Zdroj: | PLoS ONE, Vol 13, Iss 10, p e0205514 (2018) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Hippo signaling pathway is considered a key regulator of tissue homeostasis, cell proliferation, apoptosis and it is involved in cancer development. In skeletal muscle, YAP, a downstream target of the Hippo pathway, is an important player in myoblast proliferation, atrophy/hypertrophy regulation, and in mechano-trasduction, transferring mechanical signals into transcriptional responses. We studied components of Hippo pathway in muscle specimens from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, limb-girdle muscular dystrophy type 2A and type 2B and healthy subjects. Only DMD muscles had decreased YAP1 protein expression, increased LATS1/2 kinase activity, low Survivin mRNA expression and high miR-21 expression. In light of our novel results, a schematic model is postulated: low levels of YOD1 caused by increased inhibition by miR-21 lead to an increase of LATS1/2 activity which in turn augments phosphorylation of YAP. Reduced amount of active YAP, which is also a target of increased miR-21, causes decreased nuclear expression of YAP-mediated target genes. Since it is known that YAP has beneficial roles in promoting tissue repair and regeneration after injury so that its activation may be therapeutically useful, our results suggest that some components of Hippo pathway could become novel therapeutic targets for DMD treatment. |
| Databáze: | OpenAIRE |
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