Fibroblasts from phenotypically normal palmar fascia exhibit molecular profiles highly similar to fibroblasts from active disease in Dupuytren's Contracture View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-05-04

AUTHORS

Latha Satish, William A LaFramboise, Sandra Johnson, Linda Vi, Anna Njarlangattil, Christina Raykha, John Michael Krill-Burger, Phillip H Gallo, David B O'Gorman, Bing Siang Gan, Mark E Baratz, Garth D Ehrlich, Sandeep Kathju

ABSTRACT

BackgroundDupuytren's contracture (DC) is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC.MethodsTo achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group). These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments). Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02), hierarchical clustering, concordance mapping and Venn diagram.ResultsWe found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that a collagen-rich environment differentially alters gene expression in these cells. In addition, Ingenuity pathway analysis of the specific biological pathways that differentiate DC-derived cells from carpal tunnel-derived cells has identified the potential involvement of microRNAs in this fibroproliferative disorder.ConclusionsThese data show that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected palmar fascia in DC patients are highly similar, and differ significantly from the transcriptomic profiles of fibroblasts from the palmar fascia of patients undergoing carpal tunnel release. More... »

PAGES

15

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1755-8794-5-15

DOI

http://dx.doi.org/10.1186/1755-8794-5-15

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021964342

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22559715


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25 schema:description BackgroundDupuytren's contracture (DC) is a fibroproliferative disorder characterized by the progressive development of a scar-like collagen-rich cord that affects the palmar fascia of the hand and leads to digital flexion contractures. DC is most commonly treated by surgical resection of the diseased tissue, but has a high reported recurrence rate ranging from 27% to 80%. We sought to determine if the transcriptomic profiles of fibroblasts derived from DC-affected palmar fascia, adjacent phenotypically normal palmar fascia, and non-DC palmar fascial tissues might provide mechanistic clues to understanding the puzzle of disease predisposition and recurrence in DC.MethodsTo achieve this, total RNA was obtained from fibroblasts derived from primary DC-affected palmar fascia, patient-matched unaffected palmar fascia, and palmar fascia from non-DC patients undergoing carpal tunnel release (6 patients in each group). These cells were grown on a type-1 collagen substrate (to better mimic their in vivo environments). Microarray analyses were subsequently performed using Illumina BeadChip arrays to compare the transcriptomic profiles of these three cell populations. Data were analyzed using Significance Analysis of Microarrays (SAM v3.02), hierarchical clustering, concordance mapping and Venn diagram.ResultsWe found that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected fascia of DC patients exhibited a much greater overlap than fibroblasts derived from the palmar fascia of patients undergoing carpal tunnel release. Quantitative real time RT-PCR confirmed the differential expression of select genes validating the microarray data analyses. These data are consistent with the hypothesis that predisposition and recurrence in DC may stem, at least in part, from intrinsic similarities in the basal gene expression of diseased and phenotypically unaffected palmar fascia fibroblasts. These data also demonstrate that a collagen-rich environment differentially alters gene expression in these cells. In addition, Ingenuity pathway analysis of the specific biological pathways that differentiate DC-derived cells from carpal tunnel-derived cells has identified the potential involvement of microRNAs in this fibroproliferative disorder.ConclusionsThese data show that the transcriptomic profiles of DC-disease fibroblasts and fibroblasts from unaffected palmar fascia in DC patients are highly similar, and differ significantly from the transcriptomic profiles of fibroblasts from the palmar fascia of patients undergoing carpal tunnel release.
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32 schema:keywords BeadChip array
33 ConclusionsThese data
34 DC
35 DC patients
36 Dupuytren's contracture
37 Illumina BeadChip arrays
38 Ingenuity Pathway Analysis
39 MethodsTo
40 RNA
41 RT-PCR
42 ResultsWe
43 Venn diagram
44 active disease
45 addition
46 alters gene expression
47 analysis
48 array
49 basal gene expression
50 biological pathways
51 carpal tunnel release
52 cell populations
53 cells
54 clues
55 clustering
56 collagen substrate
57 collagen-rich environment
58 contracture
59 cord
60 data
61 data analysis
62 development
63 diagram
64 differential expression
65 digital flexion contracture
66 disease
67 disease predisposition
68 diseased tissues
69 disorders
70 environment
71 expression
72 fascia
73 fascia fibroblasts
74 fascial tissue
75 fibroblasts
76 fibroproliferative disorder
77 flexion contracture
78 gene expression
79 genes
80 greater overlap
81 hand
82 hierarchical clustering
83 hypothesis
84 intrinsic similarity
85 involvement
86 mapping
87 mechanistic clues
88 microRNAs
89 microarray
90 microarray analysis
91 microarray data analysis
92 molecular profile
93 non-DC patients
94 normal palmar fascia
95 overlap
96 palmar
97 palmar fascia
98 part
99 pathway
100 pathway analysis
101 patients
102 population
103 potential involvement
104 predisposition
105 primary DCs
106 profile
107 progressive development
108 puzzle
109 quantitative real-time RT-PCR
110 rate
111 real-time RT-PCR
112 recurrence
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114 release
115 resection
116 select genes
117 significance analysis
118 similarity
119 specific biological pathways
120 substrate
121 surgical resection
122 time RT-PCR
123 tissue
124 total RNA
125 transcriptomic profiles
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