Potent pro-inflammatory and profibrotic molecules, osteopontin and galectin-3, are not major disease modulators of laminin α2 chaindeficient muscular dystrophy
Gawlik, Kinga I. LU ; Holmberg, Johan LU ; Svensson, Martina LU
; Einerborg, Mikaela
; Moreira Soares Oliveira, Bernardo
LU
; Deierborg, Tomas
LU
and Durbeej-Hjalt, Madeleine
LU
(2017)
In Scientific Reports
7.
- Abstract
A large number of human diseases are caused by chronic tissue injury with fibrosis potentially leading to organ failure. There is a need for more effective anti-fibrotic therapies. Congenital muscular dystrophy type 1A (MDC1A) is a devastating form of muscular dystrophy caused by laminin α2 chaindeficiency. It is characterized with early inflammation and build-up of fibrotic lesions, both in patients and MDC1A mouse models (e.g. dy3K/dy3K). Despite the enormous impact of inflammation on tissue remodelling in disease, the inflammatory response in MDC1A has been poorly described. Consequently, a comprehensive understanding of secondary mechanisms (impaired regeneration, enhanced fibrosis) leading to deterioration of muscle phenotype in... (More)
A large number of human diseases are caused by chronic tissue injury with fibrosis potentially leading to organ failure. There is a need for more effective anti-fibrotic therapies. Congenital muscular dystrophy type 1A (MDC1A) is a devastating form of muscular dystrophy caused by laminin α2 chaindeficiency. It is characterized with early inflammation and build-up of fibrotic lesions, both in patients and MDC1A mouse models (e.g. dy3K/dy3K). Despite the enormous impact of inflammation on tissue remodelling in disease, the inflammatory response in MDC1A has been poorly described. Consequently, a comprehensive understanding of secondary mechanisms (impaired regeneration, enhanced fibrosis) leading to deterioration of muscle phenotype in MDC1A is missing. We have monitored inflammatory processes in dy3K/dy3K muscle and created mice deficient in laminin α2 chain and osteopontin or galectin-3, two pro-inflammatory and pro-fibrotic molecules drastically increased in dystrophic muscle. Surprisingly, deletion of osteopontin worsened the phenotype of dy3K/dy3K mice and loss of galectin-3 did not reduce muscle pathology. Our results indicate that osteopontin could even be a beneficial immunomodulator in MDC1A. This knowledge is essential for the design of future therapeutic interventions for muscular dystrophies that aim at targeting inflammation, especially that osteopontin inhibition has been suggested for Duchenne muscular dystrophy therapy.
(Less)
- author
- Gawlik, Kinga I.
LU
; Holmberg, Johan
LU
; Svensson, Martina
LU
; Einerborg, Mikaela
; Moreira Soares Oliveira, Bernardo
LU
; Deierborg, Tomas
LU
and Durbeej-Hjalt, Madeleine
LU
- organization
- publishing date
- 2017-03-10
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 7
- article number
- 44059
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85015159158
- pmid:28281577
- wos:000395888800001
- ISSN
- 2045-2322
- DOI
- 10.1038/srep44059
- language
- English
- LU publication?
- yes
- id
- 4380bd15-2af6-44f0-bab6-f15371c87cad
- date added to LUP
- 2017-03-29 12:35:46
- date last changed
- 2024-07-07 15:12:18
@article{4380bd15-2af6-44f0-bab6-f15371c87cad,
abstract = {{<p>A large number of human diseases are caused by chronic tissue injury with fibrosis potentially leading to organ failure. There is a need for more effective anti-fibrotic therapies. Congenital muscular dystrophy type 1A (MDC1A) is a devastating form of muscular dystrophy caused by laminin α2 chaindeficiency. It is characterized with early inflammation and build-up of fibrotic lesions, both in patients and MDC1A mouse models (e.g. dy3K/dy3K). Despite the enormous impact of inflammation on tissue remodelling in disease, the inflammatory response in MDC1A has been poorly described. Consequently, a comprehensive understanding of secondary mechanisms (impaired regeneration, enhanced fibrosis) leading to deterioration of muscle phenotype in MDC1A is missing. We have monitored inflammatory processes in dy3K/dy3K muscle and created mice deficient in laminin α2 chain and osteopontin or galectin-3, two pro-inflammatory and pro-fibrotic molecules drastically increased in dystrophic muscle. Surprisingly, deletion of osteopontin worsened the phenotype of dy3K/dy3K mice and loss of galectin-3 did not reduce muscle pathology. Our results indicate that osteopontin could even be a beneficial immunomodulator in MDC1A. This knowledge is essential for the design of future therapeutic interventions for muscular dystrophies that aim at targeting inflammation, especially that osteopontin inhibition has been suggested for Duchenne muscular dystrophy therapy.</p>}},
author = {{Gawlik, Kinga I. and Holmberg, Johan and Svensson, Martina and Einerborg, Mikaela and Moreira Soares Oliveira, Bernardo and Deierborg, Tomas and Durbeej-Hjalt, Madeleine}},
issn = {{2045-2322}},
language = {{eng}},
month = {{03}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Potent pro-inflammatory and profibrotic molecules, osteopontin and galectin-3, are not major disease modulators of laminin α2 chaindeficient muscular dystrophy}},
url = {{http://dx.doi.org/10.1038/srep44059}},
doi = {{10.1038/srep44059}},
volume = {{7}},
year = {{2017}},
}