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RNA sequencing reveals a depletion of collagen targeting microRNAs in Dupuytren's disease.

Riester SM, Arsoy D, Camilleri ET, Dudakovic A, Paradise CR, Evans JM, Torres-Mora J, Rizzo M, Kloen P, Julio MK, van Wijnen AJ, Kakar S - BMC Med Genomics (2015)

Bottom Line: RT-qPCR confirmed the decreased expression of microRNA targeted collagens in control palmar fascia tissues.Control palmar fascia show decreased expression of mRNAs encoding collagens that are preferentially targeted by microRNAs enriched in non-diseased fascia.Dupuytren's fascia and healthy palmar fascia can be distinguished by unique microRNA profiles, which are predicted to preferentially target collagens and other extracellular matrix proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. riester.scott@mayo.edu.

ABSTRACT

Background: Dupuytren's disease is an inherited disorder in which patients develop fibrotic contractures of the hand. Current treatment strategies include surgical excision or enzymatic digestion of fibrotic tissue. MicroRNAs, which are key posttranscriptional regulators of genes expression, have been shown to play an important regulatory role in disorders of fibrosis. Therefore in this investigation, we apply high throughput next generation RNA sequencing strategies to characterize microRNA expression in diseased and healthy palmar fascia to elucidate molecular mechanisms responsible for pathogenic fibrosis.

Methods: We applied high throughput RNA sequencing techniques to quantify the expression of all known human microRNAs in Dupuytren's and control palmar fascia. MicroRNAs that were differentially expressed between diseased and healthy tissue samples were used for computational target prediction using the bioinformatics tool ComiR. Molecular pathways that were predicted to be differentially expressed based on computational analysis were validated by performing RT-qPCR on RNA extracted from diseased and non-diseased palmar fascia biopsies.

Results: A comparison of microRNAs expressed in Dupuytren's fascia and control fascia identified 74 microRNAs with a 2-fold enrichment in Dupuytren's tissue, and 32 microRNAs with enrichment in control fascia. Computational target prediction for differentially expressed microRNAs indicated preferential targeting of collagens and extracellular matrix related proteins in control palmar fascia. RT-qPCR confirmed the decreased expression of microRNA targeted collagens in control palmar fascia tissues.

Discussion: Control palmar fascia show decreased expression of mRNAs encoding collagens that are preferentially targeted by microRNAs enriched in non-diseased fascia. Thus alterations in microRNA regulatory networks may play an important role in driving the pathogenic fibrosis seen in Dupuytren's disease via direct regulatory effects on extracellular matrix protein synthesis.

Conclusion: Dupuytren's fascia and healthy palmar fascia can be distinguished by unique microRNA profiles, which are predicted to preferentially target collagens and other extracellular matrix proteins.

No MeSH data available.


Related in: MedlinePlus

Unsupervised hierarchical clustering of comprehensive microRNA sequencing reads using the Pearson correlation method results in independent clustering of Dupuytren’s and control palmar fascia. Only a single adjacent fascia specimen clustered with the Dupuytren’s fascia indicating that visual inspection alone may not be reliable in distinguishing between diseased and non-diseased fascia. These data show that microRNA expression patterns may be able to differentiate between diseased and non-diseased fascia and may play key roles in driving pathogenic fibrosis
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Fig2: Unsupervised hierarchical clustering of comprehensive microRNA sequencing reads using the Pearson correlation method results in independent clustering of Dupuytren’s and control palmar fascia. Only a single adjacent fascia specimen clustered with the Dupuytren’s fascia indicating that visual inspection alone may not be reliable in distinguishing between diseased and non-diseased fascia. These data show that microRNA expression patterns may be able to differentiate between diseased and non-diseased fascia and may play key roles in driving pathogenic fibrosis

Mentions: Unsupervised hierarchical clustering was performed using the Pearson correlation method to provide an unbiased assessment of the ability of microRNAs to differentiate between diseased and non-diseased palmar fascia biopsies (Fig. 2). The clustering dendrogram showed independent grouping of the control and diseased palmar fascia biopsies. There was only a single adjacent fascia biopsy that clustered with the Dupuytren’s specimens suggesting that this specimen may have in fact been diseased tissue that appeared grossly normal intra-operatively.Fig. 2


RNA sequencing reveals a depletion of collagen targeting microRNAs in Dupuytren's disease.

Riester SM, Arsoy D, Camilleri ET, Dudakovic A, Paradise CR, Evans JM, Torres-Mora J, Rizzo M, Kloen P, Julio MK, van Wijnen AJ, Kakar S - BMC Med Genomics (2015)

Unsupervised hierarchical clustering of comprehensive microRNA sequencing reads using the Pearson correlation method results in independent clustering of Dupuytren’s and control palmar fascia. Only a single adjacent fascia specimen clustered with the Dupuytren’s fascia indicating that visual inspection alone may not be reliable in distinguishing between diseased and non-diseased fascia. These data show that microRNA expression patterns may be able to differentiate between diseased and non-diseased fascia and may play key roles in driving pathogenic fibrosis
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597401&req=5

Fig2: Unsupervised hierarchical clustering of comprehensive microRNA sequencing reads using the Pearson correlation method results in independent clustering of Dupuytren’s and control palmar fascia. Only a single adjacent fascia specimen clustered with the Dupuytren’s fascia indicating that visual inspection alone may not be reliable in distinguishing between diseased and non-diseased fascia. These data show that microRNA expression patterns may be able to differentiate between diseased and non-diseased fascia and may play key roles in driving pathogenic fibrosis
Mentions: Unsupervised hierarchical clustering was performed using the Pearson correlation method to provide an unbiased assessment of the ability of microRNAs to differentiate between diseased and non-diseased palmar fascia biopsies (Fig. 2). The clustering dendrogram showed independent grouping of the control and diseased palmar fascia biopsies. There was only a single adjacent fascia biopsy that clustered with the Dupuytren’s specimens suggesting that this specimen may have in fact been diseased tissue that appeared grossly normal intra-operatively.Fig. 2

Bottom Line: RT-qPCR confirmed the decreased expression of microRNA targeted collagens in control palmar fascia tissues.Control palmar fascia show decreased expression of mRNAs encoding collagens that are preferentially targeted by microRNAs enriched in non-diseased fascia.Dupuytren's fascia and healthy palmar fascia can be distinguished by unique microRNA profiles, which are predicted to preferentially target collagens and other extracellular matrix proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedic Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. riester.scott@mayo.edu.

ABSTRACT

Background: Dupuytren's disease is an inherited disorder in which patients develop fibrotic contractures of the hand. Current treatment strategies include surgical excision or enzymatic digestion of fibrotic tissue. MicroRNAs, which are key posttranscriptional regulators of genes expression, have been shown to play an important regulatory role in disorders of fibrosis. Therefore in this investigation, we apply high throughput next generation RNA sequencing strategies to characterize microRNA expression in diseased and healthy palmar fascia to elucidate molecular mechanisms responsible for pathogenic fibrosis.

Methods: We applied high throughput RNA sequencing techniques to quantify the expression of all known human microRNAs in Dupuytren's and control palmar fascia. MicroRNAs that were differentially expressed between diseased and healthy tissue samples were used for computational target prediction using the bioinformatics tool ComiR. Molecular pathways that were predicted to be differentially expressed based on computational analysis were validated by performing RT-qPCR on RNA extracted from diseased and non-diseased palmar fascia biopsies.

Results: A comparison of microRNAs expressed in Dupuytren's fascia and control fascia identified 74 microRNAs with a 2-fold enrichment in Dupuytren's tissue, and 32 microRNAs with enrichment in control fascia. Computational target prediction for differentially expressed microRNAs indicated preferential targeting of collagens and extracellular matrix related proteins in control palmar fascia. RT-qPCR confirmed the decreased expression of microRNA targeted collagens in control palmar fascia tissues.

Discussion: Control palmar fascia show decreased expression of mRNAs encoding collagens that are preferentially targeted by microRNAs enriched in non-diseased fascia. Thus alterations in microRNA regulatory networks may play an important role in driving the pathogenic fibrosis seen in Dupuytren's disease via direct regulatory effects on extracellular matrix protein synthesis.

Conclusion: Dupuytren's fascia and healthy palmar fascia can be distinguished by unique microRNA profiles, which are predicted to preferentially target collagens and other extracellular matrix proteins.

No MeSH data available.


Related in: MedlinePlus