nach oben

Rheumatology International

Erschienen in:

01.08.2015 | Original Article - Genes and Disease

Screening of candidate genes in fibroblasts derived from patients with Dupuytren’s contracture using bioinformatics analysis

verfasst von: Haoyu Liu, Weitian Yin, Biao Liu, Yan Liu, Baofeng Guo, Zhuang Wei

Erschienen in: Rheumatology International | Ausgabe 8/2015

Einloggen, um Zugang zu erhalten

Abstract

Our study aimed to identify candidate genes associated with Dupuytren’s contracture (DC) and elucidate their roles in DC development. The microarray data of GSE21221 were downloaded from Gene Expression Omnibus database, including six samples from carpal tunnel-derived fibroblasts and six samples from DC-derived fibroblasts. The differentially expressed genes (DEGs) in DC samples were screened using limma package. GO annotation and KEGG pathway analyses were performed by DAVID online tool. Protein–protein interaction network and expression correlation network were constructed to identify crucial relationships between DEGs. Finally, candidate DC-associated genes were predicted based on comparative toxicogenomics database. A total of 529 DEGs (138 up- and 391 down-regulated) in DC-derived fibroblasts were screened and compared with carpal tunnel-derived fibroblasts. Only ten DC-associated genes, such as neurotrophin 3 (NTF3) and protein kinase C, epsilon (PRKCE), were further screened. In addition, NTF3 was significantly enriched in MAPK signaling pathway, in which other DEGs, such as nuclear receptor subfamily 4, group A, member 1 (NR4A1), fibroblast growth factor 22 (FGF22) and BDNF, were enriched. Besides, NTF3 could co-express with fibrillin 2 (FBN2), and PRKCE could co-express with zinc finger protein 516 (ZNF516), solute carrier organic anion transporter family, member 2A1 (SLCO2A1), chromosome 10 open reading frame 10 (C10orf10) and Kelch domain containing 7A (KLHDC7A). Our study indicates that these DEGs, including NTF3, FBN2, NR4A1, FGF22, BDNF, PRKCE, ZNF516, SLCO2A1, C10orf10 and KLHDC7A, may play important roles in DC development and serve as candidate molecular targets for treating DC.

Wilbrand S, Flodmark C, Ekbom A, Gerdin B (2003) Activation markers of connective tissue in Dupuytren’s contracture: relation to postoperative outcome. Scand J Plast Reconstr Surg Hand Surg 37:283–292PubMedCrossRef

Beldner S (2013) Dupuytren’s contracture. Orthopedics 36:929–930. doi:10.3928/01477447-20131120-05 PubMedCrossRef

Ryhanen J, Forsman M (2012) Dupuytren’s contracture. Duodecim 128:421–429PubMed

Krüger-Sayn M, Porzberg G, Paschmeyer H (1998) Does the open palm technique for surgery of Dupuytren’s contracture extend treatment and disability duration? A retrospective study. [Handchirurgie, Mikrochirurgie, plastische Chirurgie: Organ der Deutschsprachigen Arbeitsgemeinschaft fur Handchirurgie: Organ der Deutschsprachigen Arbeitsgemeinschaft fur Mikrochirurgie der Peripheren Nerven und Gefasse]. Organ der V 30:269–271

Shaw RB Jr, Chong AK, Zhang A, Hentz VR, Chang J (2007) Dupuytren’s disease: history, diagnosis, and treatment. Plast Reconstr Surg 120:44e–54ePubMedCrossRef

Satish L, LaFramboise WA, O’Gorman DB et al (2008) Identification of differentially expressed genes in fibroblasts derived from patients with Dupuytren’s contracture. BMC Med Genomics 1:10. doi:10.1186/1755-8794-1-10 PubMedCentralPubMedCrossRef

Pan D, Watson HK, Swigart C, Thomson JG, Honig SC, Narayan D (2003) Microarray gene analysis and expression profiles of Dupuytren’s contracture. Ann Plast Surg 50:618–622PubMedCrossRef

Bayat A, Walter J, Lambe H, Watson JS, Stanley JK, Marino M, Ferguson MW, Ollier WE (2005) Identification of a novel mitochondrial mutation in Dupuytren’s disease using multiplex DHPLC. Plast Reconstr Surg 115:134–141PubMed

Hu F, Nystrom A, Ahmed A et al (2005) Mapping of an autosomal dominant gene for Dupuytren’s contracture to chromosome 16q in a Swedish family. Clin Genet 68:424–429PubMedCrossRef

10.

Shih B, Wijeratne D, Armstrong DJ, Lindau T, Day P, Bayat A (2009) Identification of biomarkers in Dupuytren’s disease by comparative analysis of fibroblasts versus tissue biopsies in disease-specific phenotypes. J Hand Surg Am 34:124–136PubMedCrossRef

11.

Kraljevic Pavelic S, Sedic M, Hock K et al (2009) An integrated proteomics approach for studying the molecular pathogenesis of Dupuytren’s disease. J Pathol 217:524–533PubMedCrossRef

12.

Casalone R, Mazzola D, Meroni E et al (1997) Cytogenetic and interphase cytogenetic analyses reveal chromosome instability but no clonal trisomy 8 in Dupuytren contracture. Cancer Genet Cytogenet 99:73–76PubMedCrossRef

13.

Bayat A, Watson JS, Stanley JK, Ferguson MW, Ollier WE (2003) Genetic susceptibility to dupuytren disease: association of Zf9 transcription factor gene. Plast Reconstr Surg 111:2133–2139PubMedCrossRef

14.

Augoff K, Kula J, Gosk J, Rutowski R (2005) Epidermal growth factor in Dupuytren’s disease. Plast Reconstr Surg 115:128–133PubMed

15.

Hinz B, Gabbiani G (2012) The role of the myofibroblast in Dupuytren’s disease: fundamental aspects of contraction and therapeutic perspectives. In: Dupuytren’s disease and related hyperproliferative disorders. Springer, Basel, Switzerland, pp 53–60

16.

Ji X, Tian F, Tian L (2015) Identification and function analysis of contrary genes in Dupuytren’s contracture. Mol Med Rep 12:482–488PubMed

17.

Smyth GK (2005) Limma: linear models for microarray data. In: Bioinformatics and computational biology solutions using R and bioconductor. Springer, New York, pp 397–420

18.

Ashburner M, Ball CA, Blake JA et al (2000) Gene Ontology: tool for the unification of biology. Nat Genet 25:25–29PubMedCentralPubMedCrossRef

19.

Kanehisa M, Goto S (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30PubMedCentralPubMedCrossRef

20.

Alvord G, Roayaei J, Stephens R, Baseler MW, Lane HC, Lempicki RA (2007) The DAVID gene functional classification tool: a novel biological module-centric algorithm to functionally analyze large gene lists. Genome Biol 8:R183PubMedCentralPubMedCrossRef

21.

Franceschini A, Szklarczyk D, Frankild S et al (2013) STRING v9. 1: protein–protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41:D808–D815PubMedCentralPubMedCrossRef

22.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13:2498–2504PubMedCentralPubMedCrossRef

23.

Nepusz T, Yu H, Paccanaro A (2012) Detecting overlapping protein complexes in protein–protein interaction networks. Nat Methods 9:471–472PubMedCentralPubMedCrossRef

24.

Janaki C, Joshi RR (2004) Motif detection in arabidopsis: correlation with gene expression data. In Silico Biol 4:149–161PubMed

25.

Maere S, Heymans K, Kuiper M (2005) BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21:3448–3449PubMedCrossRef

26.

Davis AP, King BL, Mockus S, Murphy CG, Saraceni-Richards C, Rosenstein M, Wiegers T, Mattingly CJ (2011) The comparative toxicogenomics database: update 2011. Nucleic Acids Res 39:D1067–D1072PubMedCentralPubMedCrossRef

27.

Vaughan MB, Howard EW, Tomasek JJ (2000) Transforming growth factor-β1 promotes the morphological and functional differentiation of the myofibroblast. Exp Cell Res 257:180–189PubMedCrossRef

28.

Al-Qattan MM (2006) Factors in the pathogenesis of Dupuytren’s contracture. J Hand Surg Am 31:1527–1534PubMedCrossRef

29.

Petrov VV, Fagard RH, Lijnen PJ (2002) Stimulation of collagen production by transforming growth factor-β1 during differentiation of cardiac fibroblasts to myofibroblasts. Hypertension 39:258–263PubMedCrossRef

30.

Kuwahara F, Kai H, Tokuda K, Kai M, Takeshita A, Egashira K, Imaizumi T (2002) Transforming growth factor-β function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure-overloaded rats. Circulation 106:130–135PubMedCrossRef

31.

Horiguchi M, Ota M, Rifkin DB (2012) Matrix control of transforming growth factor-β function. J Biochem 152:321–329PubMedCentralPubMedCrossRef

32.

Wagenseil JE, Mecham RP (2007) New insights into elastic fiber assembly. Birth Defects Res C Embryo Today 81:229–240PubMedCrossRef

33.

Forrester HB, Li J, Leong T, McKay MJ, Sprung CN (2014) Identification of a radiation sensitivity gene expression profile in primary fibroblasts derived from patients who developed radiotherapy-induced fibrosis. Radiother Oncol 111:186–193PubMedCrossRef

34.

Nishimura A, Sakai H, Ikegawa S et al (2007) FBN2, FBN1, TGFBR1, and TGFBR2 analyses in congenital contractural arachnodactyly. Am J Med Genet A 143:694–698CrossRef

35.

Durany N, Michel T, Zöchling R, Boissl KW, Cruz-Sánchez FF, Riederer P, Thome J (2001) Brain-derived neurotrophic factor and neurotrophin 3 in schizophrenic psychoses. Schizophr Res 52:79–86PubMedCrossRef

36.

Howe EN, Cochrane DR, Cittelly DM, Richer JK (2012) miR-200c targets a NF-κB up-regulated TrkB/NTF3 autocrine signaling loop to enhance anoikis sensitivity in triple negative breast cancer. PLoS ONE 7:e49987PubMedCentralPubMedCrossRef

37.

Dolcet X, Llobet D, Pallares J, Matias-Guiu X (2005) NF-kB in development and progression of human cancer. Virchows Arch 446:475–482PubMedCrossRef

38.

Bonni A, Brunet A, West AE, Datta SR, Takasu MA, Greenberg ME (1999) Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms. Science 286:1358–1362PubMedCrossRef

39.

Hirano S, Rees RS, Gilmont RR (2002) MAP kinase pathways involving hsp27 regulate fibroblast-mediated wound contraction. J Surg Res 102:77–84PubMedCrossRef

40.

Krause C, Kloen P, ten Dijke P (2011) Elevated transforming growth factor B and mitogen-activated protein kinase pathways mediate fibrotic traits of Dupuytren’s disease fibroblasts. Fibrogenesis Tissue Repair 4:14PubMedCentralPubMedCrossRef

41.

Smith AG, Lim W, Pearen M, Muscat GE, Sturm RA (2011) Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells. Pigment Cell Melanoma Res 24:551–563PubMedCrossRef

42.

Palumbo-Zerr K, Zerr P, Distler A et al (2015) Orphan nuclear receptor NR4A1 regulates transforming growth factor-[beta] signaling and fibrosis. Nat Med 21:150–158PubMedCrossRef

43.

Mulhall JP, Thom J, Lubrano T, Shankey TV (2001) Basic fibroblast growth factor expression in Peyronie’s disease. J Urol 165:419–423PubMedCrossRef

44.

IJzer J, Roskams T, Molenbeek RF, Ultee T, Penning LC, Rothuizen J, Van den Ingh TS (2006) Morphological characterisation of portal myofibroblasts and hepatic stellate cells in the normal dog liver. Comp Hepatol 5:1–9CrossRef

45.

Nguyen N, Lee SB, Lee YS, Lee K-H, Ahn J-Y (2009) Neuroprotection by NGF and BDNF against neurotoxin-exerted apoptotic death in neural stem cells are mediated through Trk receptors, activating PI3-kinase and MAPK pathways. Neurochem Res 34:942–951PubMedCrossRef

46.

Stawowy P, Margeta C, Blaschke F, Lindschau C, Spencer-Hänsch C, Leitges M, Biagini G, Fleck E, Graf K (2005) Protein kinase C epsilon mediates angiotensin II-induced activation of β1-integrins in cardiac fibroblasts. Cardiovasc Res 67:50–59PubMedCrossRef

47.

Bogatkevich GS, Gustilo E, Oates JC, Feghali-Bostwick C, Harley RA, Silver RM, Ludwicka-Bradley A (2005) Distinct PKC isoforms mediate cell survival and DNA synthesis in thrombin-induced myofibroblasts. Am J Physiol Lung Cell Mol Physiol 288:L190–L201PubMedCrossRef

48.

Ribas J, Michailidi C, Perez J, Soudry E, Tapiaz O, Guzman P, Munoz S (2014) Genome-wide methylation profiling reveals Zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population. Epigenetics 9:1–10CrossRef

49.

Zhang Z, Xia W, He J et al (2012) Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am J Hum Genet 90:125–132PubMedCentralPubMedCrossRef

50.

Wang J, Robinson JF, O’Neil CH, Edwards JY, Williams CM, Huff MW, Pickering JG, Hegele RA (2006) Ankyrin G overexpression in Hutchinson–Gilford progeria syndrome fibroblasts identified through biological filtering of expression profiles. J Hum Genet 51:934–942PubMedCrossRef

51.

Vidhya G, Anusha B (2014) Diaretinopathy database—a gene database for diabetic retinopathy. Bioinformation 10:235PubMedCentralPubMedCrossRef

52.

Townley W, Baker R, Sheppard N, Grobbelaar A (2006) Dupuytren’s contracture unfolded. BMJ 332:397–400PubMedCentralPubMedCrossRef

Titel: Screening of candidate genes in fibroblasts derived from patients with Dupuytren’s contracture using bioinformatics analysis
verfasst von: Haoyu Liu
Weitian Yin
Biao Liu
Yan Liu
Baofeng Guo
Zhuang Wei
Publikationsdatum: 01.08.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Rheumatology International / Ausgabe 8/2015
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-015-3276-3

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Reizdarmsyndrom: Diäten wirksamer als Medikamente

29.04.2024 Reizdarmsyndrom Nachrichten

Bei Reizdarmsyndrom scheinen Diäten, wie etwa die FODMAP-arme oder die kohlenhydratreduzierte Ernährung, effektiver als eine medikamentöse Therapie zu sein. Das hat eine Studie aus Schweden ergeben, die die drei Therapieoptionen im direkten Vergleich analysierte.

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2015

The effect of Ramadan fasting on quiescent systemic lupus erythematosus (SLE) patients’ disease activity, health quality of life and lipid profile: a pilot study

Prevalence of ankylosing spondylitis in Poland and costs generated by AS patients in the public healthcare system

Absence of salivary CCL28 in primary Sjögren’s syndrome

Elevated plasma levels of TL1A in newly diagnosed systemic lupus erythematosus patients

Polymorphisms in the glucocorticoid receptor gene and in the glucocorticoid-induced transcript 1 gene are associated with disease activity and response to glucocorticoid bridging therapy in rheumatoid arthritis