Abstract
Ullrich congenital muscular dystrophy (UCMD) is a common form of muscular dystrophy associated with defects in collagen VI. It is characterized by loss of individual muscle fibers and muscle mass and proliferation of connective and adipose tissues. We sought to investigate the mechanisms by which collagen VI regulates muscle cell survival, size, and regeneration and, in particular, the potential role of the ubiquitin-proteasome and calpain-proteolytic systems. We studied muscle biopsies of UCMD (n = 6), other myopathy (n = 12), and control patients (n = 10) and found reduced expression of atrogin-1, MURF1, and calpain-3 mRNAs in UCMD cases. Downregulation of calpain-3 was associated with changes in the nuclear immunolocalization of nuclear factor-κB. We also observed increased expression versus controls of regeneration markers at the protein and RNA levels. Satellite cell numbers did not differ in collagen VI-deficient muscle versus normal nonregenerating muscle, indicating that collagen VI does not play a key role in the maintenance of the satellite cell pool. Our results indicate that alterations in calpain-3 and nuclear factor-κB signaling pathways may contribute to muscle mass loss in UCMD muscle, whereas atrogin-1 and MURF1 are not likely to play a major role.
| Original language | English |
|---|---|
| Pages (from-to) | 894-906 |
| Number of pages | 13 |
| Journal | Journal of Neuropathology and Experimental Neurology |
| Volume | 71 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 2012 |
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Keywords
- Calpain-3
- Collagen type VI
- Extracellular matrix
- Muscle atrophy
- Muscle regeneration
- NF-κB
- Ullrich congenital muscular dystrophy
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology
- Neurology
- Cellular and Molecular Neuroscience
Cite this
Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle : Role of calpain-3 and nuclear factor-κB signaling. / Paco, Sonia; Ferrer, Isidre; Jou, Cristina; Cusí, Victoria; Corbera, Joan; Torner, Ferran; Gualandi, Francesca; Sabatelli, Patrizia; Orozco, Anna; Gómez-Foix, Anna Maria; Colomer, Jaume; Nascimento, Andres; Jimenez-Mallebrera, Cecilia.
In: Journal of Neuropathology and Experimental Neurology, Vol. 71, No. 10, 10.2012, p. 894-906.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Muscle fiber atrophy and regeneration coexist in collagen VI-deficient human muscle
T2 - Role of calpain-3 and nuclear factor-κB signaling
AU - Paco, Sonia
AU - Ferrer, Isidre
AU - Jou, Cristina
AU - Cusí, Victoria
AU - Corbera, Joan
AU - Torner, Ferran
AU - Gualandi, Francesca
AU - Sabatelli, Patrizia
AU - Orozco, Anna
AU - Gómez-Foix, Anna Maria
AU - Colomer, Jaume
AU - Nascimento, Andres
AU - Jimenez-Mallebrera, Cecilia
PY - 2012/10
Y1 - 2012/10
N2 - Ullrich congenital muscular dystrophy (UCMD) is a common form of muscular dystrophy associated with defects in collagen VI. It is characterized by loss of individual muscle fibers and muscle mass and proliferation of connective and adipose tissues. We sought to investigate the mechanisms by which collagen VI regulates muscle cell survival, size, and regeneration and, in particular, the potential role of the ubiquitin-proteasome and calpain-proteolytic systems. We studied muscle biopsies of UCMD (n = 6), other myopathy (n = 12), and control patients (n = 10) and found reduced expression of atrogin-1, MURF1, and calpain-3 mRNAs in UCMD cases. Downregulation of calpain-3 was associated with changes in the nuclear immunolocalization of nuclear factor-κB. We also observed increased expression versus controls of regeneration markers at the protein and RNA levels. Satellite cell numbers did not differ in collagen VI-deficient muscle versus normal nonregenerating muscle, indicating that collagen VI does not play a key role in the maintenance of the satellite cell pool. Our results indicate that alterations in calpain-3 and nuclear factor-κB signaling pathways may contribute to muscle mass loss in UCMD muscle, whereas atrogin-1 and MURF1 are not likely to play a major role.
AB - Ullrich congenital muscular dystrophy (UCMD) is a common form of muscular dystrophy associated with defects in collagen VI. It is characterized by loss of individual muscle fibers and muscle mass and proliferation of connective and adipose tissues. We sought to investigate the mechanisms by which collagen VI regulates muscle cell survival, size, and regeneration and, in particular, the potential role of the ubiquitin-proteasome and calpain-proteolytic systems. We studied muscle biopsies of UCMD (n = 6), other myopathy (n = 12), and control patients (n = 10) and found reduced expression of atrogin-1, MURF1, and calpain-3 mRNAs in UCMD cases. Downregulation of calpain-3 was associated with changes in the nuclear immunolocalization of nuclear factor-κB. We also observed increased expression versus controls of regeneration markers at the protein and RNA levels. Satellite cell numbers did not differ in collagen VI-deficient muscle versus normal nonregenerating muscle, indicating that collagen VI does not play a key role in the maintenance of the satellite cell pool. Our results indicate that alterations in calpain-3 and nuclear factor-κB signaling pathways may contribute to muscle mass loss in UCMD muscle, whereas atrogin-1 and MURF1 are not likely to play a major role.
KW - Calpain-3
KW - Collagen type VI
KW - Extracellular matrix
KW - Muscle atrophy
KW - Muscle regeneration
KW - NF-κB
KW - Ullrich congenital muscular dystrophy
UR - http://www.scopus.com/inward/record.url?scp=84866728930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866728930&partnerID=8YFLogxK
U2 - 10.1097/NEN.0b013e31826c6f7b
DO - 10.1097/NEN.0b013e31826c6f7b
M3 - Article
C2 - 22975586
AN - SCOPUS:84866728930
VL - 71
SP - 894
EP - 906
JO - American Journal of Psychotherapy
JF - American Journal of Psychotherapy
SN - 0002-9564
IS - 10
ER -