Limits...
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

RT-qPCR evaluation of ten selected collagens in Dupuytren’s and control palmar fascia are shown. COL8A1 and COL15A1 are the only collagens that do not show a statistically significant enrichment in Dupuytren’s fascia. These findings are in accordance with ComiR predictions, which show that these two exhibit the lowest degree of inhibitory microRNA targeting in control fascia
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig7: RT-qPCR evaluation of ten selected collagens in Dupuytren’s and control palmar fascia are shown. COL8A1 and COL15A1 are the only collagens that do not show a statistically significant enrichment in Dupuytren’s fascia. These findings are in accordance with ComiR predictions, which show that these two exhibit the lowest degree of inhibitory microRNA targeting in control fascia

Mentions: Since extracellular matrix synthesis is predicted to be inhibited by microRNAs enriched in control palmar fascia, we examined the expression of collagens, the primary constituents of extracellular matrix in palmar fascia. We performed RT-qPCR to evaluate the expression of selected collagens linked to fibrosis in diseased and non-diseased tissues (Fig. 7). We then examined which of these collagens were preferentially targeted for microRNA inhibition in control palmar fascia based on ComiR analysis (Table 2). RT-qPCR of fibrosis related collagens shows that collagens predicted to be targeted by microRNA inhibition in controls are enriched in Dupuytren’s fascia, while collagens with less microRNA targeting (e.g. COL15A1 and COL18A1) do not show statistically significant differences in expression between diseased and non-diseased tissue. These results show that the expression of collagen targeting microRNAs inversely correlates with the expression of fibrosis related collagens in palmar fascia.Fig. 7


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)

RT-qPCR evaluation of ten selected collagens in Dupuytren’s and control palmar fascia are shown. COL8A1 and COL15A1 are the only collagens that do not show a statistically significant enrichment in Dupuytren’s fascia. These findings are in accordance with ComiR predictions, which show that these two exhibit the lowest degree of inhibitory microRNA targeting in control fascia
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig7: RT-qPCR evaluation of ten selected collagens in Dupuytren’s and control palmar fascia are shown. COL8A1 and COL15A1 are the only collagens that do not show a statistically significant enrichment in Dupuytren’s fascia. These findings are in accordance with ComiR predictions, which show that these two exhibit the lowest degree of inhibitory microRNA targeting in control fascia
Mentions: Since extracellular matrix synthesis is predicted to be inhibited by microRNAs enriched in control palmar fascia, we examined the expression of collagens, the primary constituents of extracellular matrix in palmar fascia. We performed RT-qPCR to evaluate the expression of selected collagens linked to fibrosis in diseased and non-diseased tissues (Fig. 7). We then examined which of these collagens were preferentially targeted for microRNA inhibition in control palmar fascia based on ComiR analysis (Table 2). RT-qPCR of fibrosis related collagens shows that collagens predicted to be targeted by microRNA inhibition in controls are enriched in Dupuytren’s fascia, while collagens with less microRNA targeting (e.g. COL15A1 and COL18A1) do not show statistically significant differences in expression between diseased and non-diseased tissue. These results show that the expression of collagen targeting microRNAs inversely correlates with the expression of fibrosis related collagens in palmar fascia.Fig. 7

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