Osteopontin is highly expressed in severely dystrophic muscle and seems to play a role in muscle regeneration and fibrosis

Zanotti, Simona; Gibertini, Sara; Blasi, Carlos Hernández; Cappelletti, Cristina; Bernasconi, Pia; Mantegazza, Renato; Morandi, Lucia; Mora, Marina

doi:10.1111/j.1365-2559.2011.04051.x

Cited by 59 publications

(51 citation statements)

References 50 publications

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“…Associations of miRNA (miR-21, miR-29a, miR-29c) expression levels with levels of collagen I and VI transcripts and proteins (considered markers of fibrosis, [61]), and patient age (considered an indicator of disease progression [18]), were assessed by Pearson's linear regression analysis.…”

Section: Methodsmentioning

confidence: 99%

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Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

Zanotti¹,

Gibertini²,

Curcio³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition.

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Section: Methodsmentioning

confidence: 99%

“…We found that miR-21 was upregulated in DMD muscle, and that levels correlated directly with COL1A1 and COL6A1 transcript levels (markers of fibrosis, [61]) and also age (marker of disease progression [18]). …”

Section: Mir-21 Upregulation and Its Implicationsmentioning

confidence: 96%

Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

Zanotti¹,

Gibertini²,

Curcio³

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…Osteopontin has been described as a component of the inflammatory milieu of dystrophin-deficient muscles (Haslett et al 2002;Porter et al 2002;Uaesoontrachoon et al 2008;Zanotti et al 2011), and muscles of individuals with dystrophies caused by deficiencies of other proteins (Turk et al 2006). As osteopontin promotes inflammation and fibrosis in a wide range of tissues (Mori et al 2008;Pardo et al 2005), Spencer and colleagues tested the hypothesis that osteopontin may influence inflammation and fibrosis in dystrophin deficient muscles by crossing dystrophin-deficient mdx mice with osteopontin-null mice to produce double mutant mice (DMM), lacking both dystrophin and osteopontin (Vetrone et al 2009).…”

Section: Osteopontin and Disease Severity In Duchenne Muscular Dystrophymentioning

confidence: 99%

Osteopontin, inflammation and myogenesis: influencing regeneration, fibrosis and size of skeletal muscle

Pagel

Wijesinghe

Esfandouni

et al. 2013

J. Cell Commun. Signal.

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“…Expression of OPN was demonstrated in chondrocytes [19], fibroblasts [20], dendritic cells, macrophages and T-cells [21], hepatocytes [22], smooth muscle cells [23], skeletal muscle [24], endothelial cells [25], inner ear [26], brain [27], placenta and mammary glands [28] or kidney [29], and the protein may be assayed in some biological fluids, including blood, urine, milk and semen [1,18].…”

Section: Objectivementioning

confidence: 99%

Physiological and pathophysiological implications of osteopontin and the diagnostic utility of the protein in kidney diseases

Dobrek¹

2018

J Pre Clin Clin Res.

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Introduction and objective. Osteopontin (OPN) is a protein playing many pleiotropic both physiological and pathophysiological roles in various organs. The paper briefly characterizes both the positive and negative roles of OPN, with particular emphasis on the role of the protein in kidney functioning. Brief description of the state of knowledge. As its name suggests, OPN is a protein mainly regulating bone homeostasis, but it also participates in the pathogenesis of inflammation, neoplasm, atherosclerosis and vascular calcification. OPN is also an important protein involved in kidney physiology. Its main physiological function is to act as an inhibitor of the crystallization of urine mineral components and to prevent kidney stones formation. OPN is also overproduced in various kidney pathologies (tubulointerstitial fibrosis, crescending glomerulonephritis, cyclosporine or diabetic nephropathy, renal ischemia reperfusion injury), and both experimental and clinical studies suggest that OPN may exert either a protective or detrimental effect on kidneys. Conclusions. Considering the OPN role in kidneys, the protein is currently proposed as one of novel laboratory biomarkers for renal function. OPN, along with the other proteins found in the urine in various kidney diseases (neutrophil gelatinaseassociated lipocalin-1, kidney injury molecule-1, and fatty acid binding protein) is a part of the laboratory panel that will be gradually introduced into common laboratory practice.

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Osteopontin is highly expressed in severely dystrophic muscle and seems to play a role in muscle regeneration and fibrosis

Cited by 59 publications

References 50 publications

Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy

Osteopontin, inflammation and myogenesis: influencing regeneration, fibrosis and size of skeletal muscle

Physiological and pathophysiological implications of osteopontin and the diagnostic utility of the protein in kidney diseases

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