Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury

A. Piccioni, E. Gaetani, M. Palladino, I. Gatto, R. C. Smith, V. Neri, M. Marcantoni, I. Giarretta, M. Silver, S. Straino, M. Capogrossi, R. Landolfi, R. Pola

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.

Original languageEnglish
Pages (from-to)413-421
Number of pages9
JournalGene Therapy
Volume21
Issue number4
DOIs
Publication statusPublished - 2014

Fingerprint

Hedgehogs
Genetic Therapy
Skeletal Muscle
Inbred mdx Mouse
Wounds and Injuries
Muscle Development
Muscle Cells
Regeneration
Muscles
Duchenne Muscular Dystrophy
Fibroblast Growth Factors
Somatomedins
Vascular Endothelial Growth Factor A
Embryonic Development
Plasmids
Fibrosis
Up-Regulation
Fibroblasts
Pathology
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Piccioni, A., Gaetani, E., Palladino, M., Gatto, I., Smith, R. C., Neri, V., ... Pola, R. (2014). Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury. Gene Therapy, 21(4), 413-421. https://doi.org/10.1038/gt.2014.13

Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury. / Piccioni, A.; Gaetani, E.; Palladino, M.; Gatto, I.; Smith, R. C.; Neri, V.; Marcantoni, M.; Giarretta, I.; Silver, M.; Straino, S.; Capogrossi, M.; Landolfi, R.; Pola, R.

In: Gene Therapy, Vol. 21, No. 4, 2014, p. 413-421.

Research output: Contribution to journalArticle

Piccioni, A, Gaetani, E, Palladino, M, Gatto, I, Smith, RC, Neri, V, Marcantoni, M, Giarretta, I, Silver, M, Straino, S, Capogrossi, M, Landolfi, R & Pola, R 2014, 'Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury', Gene Therapy, vol. 21, no. 4, pp. 413-421. https://doi.org/10.1038/gt.2014.13
Piccioni, A. ; Gaetani, E. ; Palladino, M. ; Gatto, I. ; Smith, R. C. ; Neri, V. ; Marcantoni, M. ; Giarretta, I. ; Silver, M. ; Straino, S. ; Capogrossi, M. ; Landolfi, R. ; Pola, R. / Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury. In: Gene Therapy. 2014 ; Vol. 21, No. 4. pp. 413-421.
@article{3185793a9aa747ca8cb1a4bbd6c44e5a,
title = "Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury",
abstract = "The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.",
author = "A. Piccioni and E. Gaetani and M. Palladino and I. Gatto and Smith, {R. C.} and V. Neri and M. Marcantoni and I. Giarretta and M. Silver and S. Straino and M. Capogrossi and R. Landolfi and R. Pola",
year = "2014",
doi = "10.1038/gt.2014.13",
language = "English",
volume = "21",
pages = "413--421",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Sonic hedgehog gene therapy increases the ability of the dystrophic skeletal muscle to regenerate after injury

AU - Piccioni, A.

AU - Gaetani, E.

AU - Palladino, M.

AU - Gatto, I.

AU - Smith, R. C.

AU - Neri, V.

AU - Marcantoni, M.

AU - Giarretta, I.

AU - Silver, M.

AU - Straino, S.

AU - Capogrossi, M.

AU - Landolfi, R.

AU - Pola, R.

PY - 2014

Y1 - 2014

N2 - The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.

AB - The Hedgehog (Hh) pathway is a crucial regulator of muscle development during embryogenesis. We have previously demonstrated that Sonic hedgehog (Shh) regulates postnatal myogenesis in the adult skeletal muscle both directly, by acting on muscle satellite cells, and indirectly, by promoting the production of growth factors from interstitial fibroblasts. Here, we show that in mdx mice, the murine equivalent of Duchenne muscular dystrophy in humans, progression of the dystrophic pathology corresponds to progressive inhibition of the Hh signaling pathway in the skeletal muscle. We also show that the upregulation of the Hh pathway in response to injury and during regeneration is significantly impaired in mdx muscle. Shh treatment increases the proliferative potential of satellite cells isolated from the muscles of mdx mice. This treatment also increases the production of proregenerative factors, such as insulin-like growth factor-1 and vascular endothelial growth factor, from fibroblasts isolated from the muscle of mdx mice. In vivo, overexpression of the Hh pathway using a plasmid encoding the human Shh gene promotes successful regeneration after injury in terms of increased number of proliferating myogenic cells and newly formed myofibers, as well as enhanced vascularization and decreased fibrosis.

UR - http://www.scopus.com/inward/record.url?scp=84897576456&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897576456&partnerID=8YFLogxK

U2 - 10.1038/gt.2014.13

DO - 10.1038/gt.2014.13

M3 - Article

VL - 21

SP - 413

EP - 421

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 4

ER -