Open AccessHippo signaling pathway is altered in Duchenne muscular dystrophy
Author(s) -
Gian Luca Vita,
Francesca Polito,
Rosaria Oteri,
Roberto Arrigo,
Anna Maria Ciranni,
Olimpia Musumeci,
Sonia Messina,
Carmelo Rodolico,
Rosa María Di Giorgio,
Giuseppe Vita,
M. Aguennouz
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205514
Subject(s) - hippo signaling pathway , yap1 , duchenne muscular dystrophy , microbiology and biotechnology , biology , regeneration (biology) , muscular dystrophy , skeletal muscle , signal transduction , cancer research , myocyte , endocrinology , transcription factor , gene , genetics
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.