Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy
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BioMed Central
Open Access
Research article
Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy Caterina Millino1,2, Marina Fanin3,4, Andrea Vettori2, Paolo Laveder2, Maria Luisa Mostacciuolo2, Corrado Angelini3,4 and Gerolamo Lanfranchi*1,2 Address: 1CRIBI Biotechnology Centre, 35121 Padova, University of Padova, Italy, 2Department of Biology Via Bassi, 35121 Padova, University of Padova, Italy, 3Department of Neurosciences, Via Giustiniani, 35128 Padova, University of Padova, Italy and 4Venetian Institute for Molecular Medicine, Via Orus, 35129 Padova, Italy Email: Caterina Millino - [email protected]; Marina Fanin - [email protected]; Andrea Vettori - [email protected]; Paolo Laveder - [email protected]; Maria Luisa Mostacciuolo - [email protected]; Corrado Angelini - [email protected]; Gerolamo Lanfranchi* - [email protected] * Corresponding author
Published: 7 April 2009 BMC Medicine 2009, 7:14
doi:10.1186/1741-7015-7-14
Received: 25 February 2009 Accepted: 7 April 2009
This article is available from: http://www.biomedcentral.com/1741-7015/7/14 © 2009 Millino et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: Spinal muscular atrophy (SMA) is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue. Methods: We applied microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe type I and the mild type III. Results: The two forms of SMA generated distinct expression signatures: the SMA III muscle transcriptome is close to that found under normal conditions, whereas in SMA I there is strong alteration of gene expression. Genes implicated in signal transduction were up-regulated in SMA III whereas those of energy metabolism and muscle contraction were consistently down-regulated in SMA I. The expression pattern of gene networks involved in atrophy signaling was completed by qRT-PCR, showing that specific pathways are involved, namely IGF/PI3K/Akt, TNF-α/p38 MAPK and Ras/ERK pathways. Conclusion: Our study suggests a different picture of atrophy pathways in each of the two forms of SMA. In particular, p38 may be the regulator of protein synthesis in SMA I. The SMA III profile appears as the result of the concurrent presence of atrophic and hypertrophic fibers. This more favorable condition might be due to the over-expression of MTOR that, given its role in the activation of pro
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