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Entrapment neuropathy results in different microRNA expression patterns from denervation injury in rats.

Rau CS, Jeng JC, Jeng SF, Lu TH, Chen YC, Liliang PC, Wu CJ, Lin CJ, Hsieh CH - BMC Musculoskelet Disord (2010)

Bottom Line: In the DRGs, 6 miRNAs in the entrapment group (miR-9, miR-320, miR-324-3p, miR-672, miR-466b, and miR-144) and 3 miRNAs in the decompression group (miR-9, miR-320, and miR-324-3p) were significantly downregulated.Regarding the muscle-specific miRNAs, real-time RT-PCR analysis revealed an approximately 50% decrease in miR-1 and miR-133a expression levels at 3 and 6 months after entrapment, whereas miR-1 and miR-133a levels were unchanged and were decreased after decompression at 1 and 3 months.In contrast, there were no statistical differences in the expression of miR-206 during nerve entrapment and after decompression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.

ABSTRACT

Background: To compare the microRNA (miRNA) expression profiles in neurons and innervated muscles after sciatic nerve entrapment using a non-constrictive silastic tube, subsequent surgical decompression, and denervation injury.

Methods: The experimental L4-L6 spinal segments, dorsal root ganglia (DRGs), and soleus muscles from each experimental group (sham control, denervation, entrapment, and decompression) were analyzed using an Agilent rat miRNA array to detect dysregulated miRNAs. In addition, muscle-specific miRNAs (miR-1, -133a, and -206) and selectively upregulated miRNAs were subsequently quantified using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR).

Results: In the soleus muscles, 37 of the 47 miRNAs (13.4% of the 350 unique miRNAs tested) that were significantly downregulated after 6 months of entrapment neuropathy were also among the 40 miRNAs (11.4% of the 350 unique miRNAs tested) that were downregulated after 3 months of decompression. No miRNA was upregulated in both groups. In contrast, only 3 miRNAs were upregulated and 3 miRNAs were downregulated in the denervated muscle after 6 months. In the DRGs, 6 miRNAs in the entrapment group (miR-9, miR-320, miR-324-3p, miR-672, miR-466b, and miR-144) and 3 miRNAs in the decompression group (miR-9, miR-320, and miR-324-3p) were significantly downregulated. No miRNA was upregulated in both groups. We detected 1 downregulated miRNA (miR-144) and 1 upregulated miRNA (miR-21) after sciatic nerve denervation. We were able to separate the muscle or DRG samples into denervation or entrapment neuropathy by performing unsupervised hierarchal clustering analysis. Regarding the muscle-specific miRNAs, real-time RT-PCR analysis revealed an approximately 50% decrease in miR-1 and miR-133a expression levels at 3 and 6 months after entrapment, whereas miR-1 and miR-133a levels were unchanged and were decreased after decompression at 1 and 3 months. In contrast, there were no statistical differences in the expression of miR-206 during nerve entrapment and after decompression. The expression of muscle-specific miRNAs in entrapment neuropathy is different from our previous observations in sciatic nerve denervation injury.

Conclusions: This study revealed the different involvement of miRNAs in neurons and innervated muscles after entrapment neuropathy and denervation injury, and implied that epigenetic regulation is different in these two conditions.

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Related in: MedlinePlus

Hierarchical cluster analysis. Using a hierarchical method, a clustering graph was created from those miRNAs with increased (red) or decreased (blue) fold of expression from 3 soleus muscles (left graph) and dorsal root ganglia (right graph) in the group of rats that sustained denervation for 6 months, entrapment for 6 months, or decompression for 3 months against those from the sham control group.
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Figure 1: Hierarchical cluster analysis. Using a hierarchical method, a clustering graph was created from those miRNAs with increased (red) or decreased (blue) fold of expression from 3 soleus muscles (left graph) and dorsal root ganglia (right graph) in the group of rats that sustained denervation for 6 months, entrapment for 6 months, or decompression for 3 months against those from the sham control group.

Mentions: miRNA array analysis indicated that approximately 13.4% (n = 47) and 11.4% (n = 40) of all rat miRNAs tested (350 unique miRNAs) were significantly decreased at 6 months of entrapment neuropathy and at 3 months after decompression, respectively, in the soleus muscle (Additional file 1: Table S1). Notably, there were 37 overlapping miRNAs under these 2 conditions and no miRNAs were upregulated in the soleus muscles of these 2 groups. Surgical decompression appeared to not remarkably alter the general expression of the downregulated miRNAs in the innervated muscle in entrapment neuropathy. In contrast, 3 miRNAs (miR-499, miR-1, miR-133a, and miR-466b) were upregulated in the denervated muscle and 3 miRNAs (miR-329, miR-204, and miR-139-3p) were downregulated after 6 months. A hierarchical cluster analysis of all significantly dysregulated miRNAs is shown in Figure 1, illustrative of miRNAs differentially expressed under these 3 conditions. We were able to separate the samples into denervation, entrapment, and decompression by performing unsupervised hierarchal clustering analysis.


Entrapment neuropathy results in different microRNA expression patterns from denervation injury in rats.

Rau CS, Jeng JC, Jeng SF, Lu TH, Chen YC, Liliang PC, Wu CJ, Lin CJ, Hsieh CH - BMC Musculoskelet Disord (2010)

Hierarchical cluster analysis. Using a hierarchical method, a clustering graph was created from those miRNAs with increased (red) or decreased (blue) fold of expression from 3 soleus muscles (left graph) and dorsal root ganglia (right graph) in the group of rats that sustained denervation for 6 months, entrapment for 6 months, or decompression for 3 months against those from the sham control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927509&req=5

Figure 1: Hierarchical cluster analysis. Using a hierarchical method, a clustering graph was created from those miRNAs with increased (red) or decreased (blue) fold of expression from 3 soleus muscles (left graph) and dorsal root ganglia (right graph) in the group of rats that sustained denervation for 6 months, entrapment for 6 months, or decompression for 3 months against those from the sham control group.
Mentions: miRNA array analysis indicated that approximately 13.4% (n = 47) and 11.4% (n = 40) of all rat miRNAs tested (350 unique miRNAs) were significantly decreased at 6 months of entrapment neuropathy and at 3 months after decompression, respectively, in the soleus muscle (Additional file 1: Table S1). Notably, there were 37 overlapping miRNAs under these 2 conditions and no miRNAs were upregulated in the soleus muscles of these 2 groups. Surgical decompression appeared to not remarkably alter the general expression of the downregulated miRNAs in the innervated muscle in entrapment neuropathy. In contrast, 3 miRNAs (miR-499, miR-1, miR-133a, and miR-466b) were upregulated in the denervated muscle and 3 miRNAs (miR-329, miR-204, and miR-139-3p) were downregulated after 6 months. A hierarchical cluster analysis of all significantly dysregulated miRNAs is shown in Figure 1, illustrative of miRNAs differentially expressed under these 3 conditions. We were able to separate the samples into denervation, entrapment, and decompression by performing unsupervised hierarchal clustering analysis.

Bottom Line: In the DRGs, 6 miRNAs in the entrapment group (miR-9, miR-320, miR-324-3p, miR-672, miR-466b, and miR-144) and 3 miRNAs in the decompression group (miR-9, miR-320, and miR-324-3p) were significantly downregulated.Regarding the muscle-specific miRNAs, real-time RT-PCR analysis revealed an approximately 50% decrease in miR-1 and miR-133a expression levels at 3 and 6 months after entrapment, whereas miR-1 and miR-133a levels were unchanged and were decreased after decompression at 1 and 3 months.In contrast, there were no statistical differences in the expression of miR-206 during nerve entrapment and after decompression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.

ABSTRACT

Background: To compare the microRNA (miRNA) expression profiles in neurons and innervated muscles after sciatic nerve entrapment using a non-constrictive silastic tube, subsequent surgical decompression, and denervation injury.

Methods: The experimental L4-L6 spinal segments, dorsal root ganglia (DRGs), and soleus muscles from each experimental group (sham control, denervation, entrapment, and decompression) were analyzed using an Agilent rat miRNA array to detect dysregulated miRNAs. In addition, muscle-specific miRNAs (miR-1, -133a, and -206) and selectively upregulated miRNAs were subsequently quantified using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR).

Results: In the soleus muscles, 37 of the 47 miRNAs (13.4% of the 350 unique miRNAs tested) that were significantly downregulated after 6 months of entrapment neuropathy were also among the 40 miRNAs (11.4% of the 350 unique miRNAs tested) that were downregulated after 3 months of decompression. No miRNA was upregulated in both groups. In contrast, only 3 miRNAs were upregulated and 3 miRNAs were downregulated in the denervated muscle after 6 months. In the DRGs, 6 miRNAs in the entrapment group (miR-9, miR-320, miR-324-3p, miR-672, miR-466b, and miR-144) and 3 miRNAs in the decompression group (miR-9, miR-320, and miR-324-3p) were significantly downregulated. No miRNA was upregulated in both groups. We detected 1 downregulated miRNA (miR-144) and 1 upregulated miRNA (miR-21) after sciatic nerve denervation. We were able to separate the muscle or DRG samples into denervation or entrapment neuropathy by performing unsupervised hierarchal clustering analysis. Regarding the muscle-specific miRNAs, real-time RT-PCR analysis revealed an approximately 50% decrease in miR-1 and miR-133a expression levels at 3 and 6 months after entrapment, whereas miR-1 and miR-133a levels were unchanged and were decreased after decompression at 1 and 3 months. In contrast, there were no statistical differences in the expression of miR-206 during nerve entrapment and after decompression. The expression of muscle-specific miRNAs in entrapment neuropathy is different from our previous observations in sciatic nerve denervation injury.

Conclusions: This study revealed the different involvement of miRNAs in neurons and innervated muscles after entrapment neuropathy and denervation injury, and implied that epigenetic regulation is different in these two conditions.

Show MeSH
Related in: MedlinePlus