Laminin-rich blood vessels display activated growth factor signaling and act as the proliferation centers in Dupuytren’s contractureReport as inadecuate

Laminin-rich blood vessels display activated growth factor signaling and act as the proliferation centers in Dupuytren’s contracture - Download this document for free, or read online. Document in PDF available to download.

Arthritis Research and Therapy

, 17:144

First Online: 28 May 2015Received: 12 February 2015Accepted: 22 May 2015


IntroductionDupuytren’s contracture DC is a chronic fibroproliferative disease of the hand, which is characterized by uncontrolled proliferation of atypical myofibroblasts at the cellular level. We hypothesized that specific areas of the DC tissue are sustaining the cell proliferation and studied the potential molecular determinants that might contribute to the formation of such niches.

MethodsWe studied the expression pattern of cell proliferation marker Ki67, phosphorylated AKT Ak mouse strain thymoma kinase, DC-associated growth factors connective tissue growth factor CTGF, basic fibroblast growth factor bFGF, insulin-like growth factor 2 IGF-2 and extracellular matrix components laminins, fibronectin, collagen IV in DC tissue and normal palmar fascia using immunofluorescence microscopy and quantitative real-time polymerase chain reaction qPCR.

ResultsWe found that proliferative cells in the DC nodules were concentrated in the immediate vicinity of small blood vessels and localized predominantly in the myofibroblast layer. Correspondingly, the DC-associated blood vessels contained increased levels of phosphorylated AKT, a hallmark of activated growth factor signaling. When studying the expression of potential activators of AKT signaling we found that the expression of bFGF was confined to the endothelium of the small blood vessels, IGF-2 was present uniformly in the DC tissue and CTGF was expressed in the DC-associated sweat gland acini. In addition, the blood vessels in DC nodules contained increased amounts of laminins 511 and 521, which have been previously shown to promote the proliferation and stem cell properties of different cell types.

ConclusionsBased on our findings, we propose that in the DC-associated small blood vessels the presence of growth factors in combination with favorable extracellular matrix composition provide a supportive environment for sustained proliferation of myofibroblasts and thus the blood vessels play an important role in DC pathogenesis.

AbbreviationsAKTAk mouse strain thymoma-associated

bFGFbasic fibroblast growth factor

cDNAcomplementary DNA

CoIVcollagen IV

CTGFconnective tissue growth factor

DCDupuytren’s contracture

ECMextracellular matrix

FITCfluorescein isothiocyanate


hESChuman embryonic stem cells

IGF-2insulin-like growth factor 2

K15cytokeratin 15

MAPKmitogen-activated protein kinase

NPFnormal palmar fascia

pAKTphosphorylated AKT

PBSphosphate-buffered saline

qPCRquantitative polymerase chain reaction

SMAsmooth muscle actin

TGF-βtransforming growth factor β

vWFvon Willebrand’s factor

Electronic supplementary materialThe online version of this article doi:10.1186-s13075-015-0661-y contains supplementary material, which is available to authorized users.

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Author: Janeli Viil - Katre Maasalu - Kristina Mäemets-Allas - Liis Tamming - Kadi Lõhmussaar - Mikk Tooming - Sulev Ingerpuu - A


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