Overexpression of SMPX in Adult Skeletal Muscle Does not Change Skeletal Muscle Fiber Type or Size

Eftestøl, Einar; Alver, Tine Norman; Gundersen, Kristian; Bruusgaard, Jo C.

doi:10.1371/journal.pone.0099232

Cited by 10 publications

(9 citation statements)

References 24 publications

(41 reference statements)

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“…We investigated the possible effects of smpx upregulation via a synthetic mRNA microinjection on both ear and muscle fibers. The increase in the amount of the protein was not associated with any developmental phenotype ( Figure S1B,D,F and data not shown), as also previously reported in rat muscles [ 26 ]. Moreover, although we never detected Smpx in the nucleus of the cells by means of protein-specific antibodies ([ 4 ] and this manuscript), as previously suggested [ 37 ], we chose to deepen our knowledge concerning the subcellular localization of Smpx, which might be critical to the understanding of Smpx biological activities, probing the position of the protein in vivo using GFP as a reporter.…”

Section: Resultssupporting

confidence: 88%

“…Therefore, the loss of function has been suggested to be the mechanism triggering hearing impairment in SMPX patients [ 18 ]. However, the effects of SMPX misregulation on otic development have never been investigated in all in-vivo models generated until now [ 9 , 26 ]. In this study, we employ zebrafish to mimic the lack of functional SMPX, representative of the condition in the inner ear hair cells of patients, through the downregulation of smpx by means of two gene-specific Morpholino antisense oligomers.…”

Section: Introductionmentioning

confidence: 99%

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Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

Ghilardi

Diana

Bacchetta

et al. 2021

IJMS

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The last decade has witnessed the identification of several families affected by hereditary non-syndromic hearing loss (NSHL) caused by mutations in the SMPX gene and the loss of function has been suggested as the underlying mechanism. In the attempt to confirm this hypothesis we generated an Smpx-deficient zebrafish model, pointing out its crucial role in proper inner ear development. Indeed, a marked decrease in the number of kinocilia together with structural alterations of the stereocilia and the kinocilium itself in the hair cells of the inner ear were observed. We also report the impairment of the mechanotransduction by the hair cells, making SMPX a potential key player in the construction of the machinery necessary for sound detection. This wealth of evidence provides the first possible explanation for hearing loss in SMPX-mutated patients. Additionally, we observed a clear muscular phenotype consisting of the defective organization and functioning of muscle fibers, strongly suggesting a potential role for the protein in the development of muscle fibers. This piece of evidence highlights the need for more in-depth analyses in search for possible correlations between SMPX mutations and muscular disorders in humans, thus potentially turning this non-syndromic hearing loss-associated gene into the genetic cause of dysfunctions characterized by more than one symptom, making SMPX a novel syndromic gene.

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Section: Resultssupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

Ghilardi

Diana

Bacchetta

et al. 2021

IJMS

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“…SMPX is a gene regulated downstream of NR4A3 and is involved in muscle regulation. The exact mechanism of SMPX isn’t currently clear, as there are conflicting studies arguing whether or not it is involved in muscle growth and differentiation (Eftestøl et al, 2014; Ferrán et al, 2016). However, there are studies suggesting that SMPX may be related to mechanical stress (Eftestøl et al, 2014), supporting the idea that increased biomechanical stress in the breast muscle may be a contributing factor to differential expression of genes between regions of the muscle and sexes of birds, as well as contributing to the development of WBD.…”

Section: Discussionmentioning

confidence: 99%

RNA-Seq Analysis Reveals Spatial and Sex Differences in Pectoralis Major Muscle of Broiler Chickens Contributing to Difference in Susceptibility to Wooden Breast Disease

2019

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Wooden Breast Disease (WBD) is a novel myopathy affecting the pectoralis major muscle of modern broiler chickens. The etiology of WBD is not currently known, but has been linked to increased feed efficiency, growth rate, and muscle yield in broiler chickens. Differential effect of WBD has been detected between regions of the P. major and between sexes of broilers—male birds and the cranial aspect of the muscle tend to be more severely affected by the disease than females and the caudal aspect. This study aimed to characterize biological differences in the P. major between regions of the muscle and sexes of birds. Samples were taken from the cranial and caudal aspects of P. major muscles of 3-week-old, unaffected male and female birds for RNA sequencing. RNA was extracted and used for preparation of cDNA libraries, which were sequenced by the Delaware Biotechnology Institute (DBI) using HiSeq2500. Sequence reads were aligned to the chicken reference genome with HISAT, and genes were analyzed for differential expression between regions of the breast muscle and sexes of birds using CuffDiff. Functional analysis was performed on differentially expressed genes (DEGs) between sex groups using DAVID and Ingenuity Pathway Analysis (IPA). There were 12 DEGs between cranial and caudal samples, and 260 between male and female birds. Out of the 260 genes differentially expressed between sexes, 189 were upregulated in males. Of this subset, 103 genes (55%) were located on the Z-chromosome. There was increased expression of genes involved in fat metabolism and oxidative stress responses in the cranial region of the P. major muscle, as well as increased expression of fat metabolism, oxidative stress response, antiangiogenesis, and connective tissue proliferation genes in male broilers. These results support the hypothesis that there are biological characteristics in male broilers and the cranial region of the breast muscle that may make them more susceptible to WBD, as well as raising the possibility of a metabolic switch in modern broiler chickens that may be more prominent in males.

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“…Other up-regulated genes related to development and regeneration of the musculosketal system include PDZ and LIM domain 3 ( PDLIM3 ), small muscle protein X-linked ( SMPX ), and leiomodin 2 ( LMOD2 ). Two of these, SMPX and PDLIM3, encode Z-disc associated proteins with putative mechanosensory or stretch signaling roles in striated muscle [114,115]. Expression of MUSTN1 , ANKRD1 , PDLIM3, and SMPX can be induced by eccentric contraction exercises [116,117,118] or passive stretch [119], suggesting a role in muscle hypertrophy and repair [115].…”

Section: Discussionmentioning

confidence: 99%

“…Two of these, SMPX and PDLIM3, encode Z-disc associated proteins with putative mechanosensory or stretch signaling roles in striated muscle [114,115]. Expression of MUSTN1 , ANKRD1 , PDLIM3, and SMPX can be induced by eccentric contraction exercises [116,117,118] or passive stretch [119], suggesting a role in muscle hypertrophy and repair [115]. Although some of these genes possess roles in muscle fiber regeneration, we do not believe that they are indicative of the regenerative process that characterizes later stages of wooden breast.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of Lipid Metabolism Genes in Early Stages of Wooden Breast Links Myopathy of Broilers to Metabolic Syndrome in Humans

Lake

Papah

Abasht

2019

Genes

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Wooden breast is a muscle disorder affecting modern commercial broiler chickens that causes a palpably firm pectoralis major muscle and severe reduction in meat quality. Most studies have focused on advanced stages of wooden breast apparent at market age, resulting in limited insights into the etiology and early pathogenesis of the myopathy. Therefore, the objective of this study was to identify early molecular signals in the wooden breast transcriptional cascade by performing gene expression analysis on the pectoralis major muscle of two-week-old birds that may later exhibit the wooden breast phenotype by market age at 7 weeks. Biopsy samples of the left pectoralis major muscle were collected from 101 birds at 14 days of age. Birds were subsequently raised to 7 weeks of age to allow sample selection based on the wooden breast phenotype at market age. RNA-sequencing was performed on 5 unaffected and 8 affected female chicken samples, selected based on wooden breast scores (0 to 4) assigned at necropsy where affected birds had scores of 2 or 3 (mildly or moderately affected) while unaffected birds had scores of 0 (no apparent gross lesions). Differential expression analysis identified 60 genes found to be significant at an FDR-adjusted p-value of 0.05. Of these, 26 were previously demonstrated to exhibit altered expression or genetic polymorphisms related to glucose tolerance or diabetes mellitus in mammals. Additionally, 9 genes have functions directly related to lipid metabolism and 11 genes are associated with adiposity traits such as intramuscular fat and body mass index. This study suggests that wooden breast disease is first and foremost a metabolic disorder characterized primarily by ectopic lipid accumulation in the pectoralis major.

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Overexpression of SMPX in Adult Skeletal Muscle Does not Change Skeletal Muscle Fiber Type or Size

Cited by 10 publications

References 24 publications

Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

Inner Ear and Muscle Developmental Defects in Smpx-Deficient Zebrafish Embryos

RNA-Seq Analysis Reveals Spatial and Sex Differences in Pectoralis Major Muscle of Broiler Chickens Contributing to Difference in Susceptibility to Wooden Breast Disease

Increased Expression of Lipid Metabolism Genes in Early Stages of Wooden Breast Links Myopathy of Broilers to Metabolic Syndrome in Humans

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