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

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.

Electronic supplementary material

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

Management Effects on Bryophytes in Estonian Forests

Bryophyte species richness and composition of six different forest types and three different management rates was analysed in 36 Estonian forests. Analyses were done separately for six different bryophyte species groups: total species number, hepatic, hemerophobic, common, non-epigeic and epigeic species. The differences in species richness between unmanaged and moderately managed forests were significant for all species groups, while the differences between moderately and intensively managed forests were significant only for total species number, and numbers of common and non-epigeic species. Our results showed also that in comparison of unmanaged and moderately managed forests, management effect was significant for species richness of all species groups except non-epigeic species, while in comparison of moderately and intensely managed forests, management rate remained significant only for total species richness and richness of common species. Also the species composition was affected by forest management. Only the compositions of unmanaged forest types were found to be significantly different between each other. In conclusion, even moderate management eliminates a significant number of bryophyte species, and the species composition of different forest types become more similar.     

Global gradients in moss and vascular plant diversity

Knowledge on the distribution and hotspots of different taxon groups is indispensable for improving the state of biodiversity protection. Our aim was to determine if the relations between major environmental factors and species richness of two plant groups, mosses and vascular plants differ on a global scale. The dependence of species richness on environmental factors in 50 regions, covering 17 % of the global terrestrial territory, was analysed with SAS statistical software. Species richness of vascular plants increases significantly towards the equator, but for mosses the increase is not significant. Species richness of mosses and vascular plants are significantly positively correlated only in the near equator zone. Although there were similarities in the trends of mosses and vascular plant diversities at a global scale, their relations with some factors differ with distance from the equator. The effect of precipitation on species richness is similar for both plant groups, but coastline length has a significant positive influence only on moss richness, whereas species richness of vascular plants was related strongly to area and energy input. Therefore, effective conservation policy at both local and global scale demands consideration of all diversity drivers of different taxon groups.     

Bryophyte vegetation in a wooded meadow: relationships with phanerogam diversity and responses to fertilisation

In the Laelatu wooded meadow in Estonia, famous for its phanerogam diversity, the bryophyte community has been investigated in order to compare its flora and diversity relationships with those of the vascular plant community. Ninety-six bryophyte species were found, 13 of them are hepatics; the majority of the bryophytes are epigeic species common to meadows and forests, including many calciphilous species. Vascular plants and bryophytes display opposite responses to fertilisation. For vascular plants, fertilisation increases the coverage and diminishes the number of species, while for bryophytes it diminishes coverage and increases the number of species. The relationship between the number of species in small plots and the total number of species in the area is similar for vascular plants and bryophytes. No significant changes in the bryophyte community in Laelatu wooded meadow has been detected during the last 30 years.     

Laminin Production and Basement Membrane Deposition by Mesenchymal Stem Cells upon Adipogenic Differentiation

The aim was to study laminin (LM) synthesis, integration, and deposition into the basement membrane (BM) during adipogenesis. Human bone marrow-derived mesenchymal stromal cells (MSCs) were induced along the adipogenic lineage. LM chain mRNA and protein levels were followed using quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence (IF) staining, transmission electron microscopy (TEM), and immunoprecipitation. MSCs produced low levels of LM mRNAs but were not surrounded by BM in IF and TEM imaging. LM-α4, LM-β1, and LM-γ1 mRNAs increased during adipogenesis 3.9-, 5.8-, and 2.8-fold by day 28. LM-411 was immunoprecipitated from the ECM of the differentiated cells. Immunostaining suggested deposition of LM-411 and some LM-421. BM build-up was probably organized in part by integrin (Int) α₆β₁. At day 28, TEM images revealed BM-like structures around fat droplet-containing cells. The first signs of BM formation and Int α₆β₁ were seen using IF imaging at day 14. Laminin-411 and Int α₆β₁ were expressed in vivo in mature human subcutaneous fat tissue. Undifferentiated human MSCs did not organize LM subunits into BM, whereas LM-411 and some LM-421 are precipitated in the BM around adipocytes. This is the first demonstration of LM-411 precipitation during hMSC adipogenesis around adipocytes as a structural scaffold and Int-regulated signaling element.     

Bryophyte and vascular plant species richness in boreo-nemoral moist forests and mires

We compare species richness of bryophytes and vascular plants in Estonian moist forests and mires. The material was collected from two wetland nature reserves. Bryophyte and vascular plant species were recorded in 338 homogeneous stands of approximately 1 ha in nine forest and two mire types. Regional species pools for bryophytes and vascular plants were significantly correlated. The correlations between the species richnesses of bryophytes and vascular plants per stand were positive in all community types. The relative richnesses (local richness divided by the regional species pool size) were similar for bryophyte species and for vascular plant species. This shows that on larger scales, conservation of the communities rich in species of one taxonomic plant group, maintains also the species richness of the other. The minimum number of stands needed for the maintenance of the regional species pool of typical species for the every community type was calculated using the species richness accumulation curves. Less stands are needed to maintain the bryophyte species pools (300–5300 for bryophytes and 400–35 000 for vascular plants).     

Changes in Laminin Expression Pattern during Early Differentiation of Human Embryonic Stem Cells

Laminin isoforms laminin-511 and -521 are expressed by human embryonic stem cells (hESC) and can be used as a growth matrix to culture these cells under pluripotent conditions. However, the expression of these laminins during the induction of hESC differentiation has not been studied in detail. Furthermore, the data regarding the expression pattern of laminin chains in differentiating hESC is scarce. In the current study we aimed to fill this gap and investigated the potential changes in laminin expression during early hESC differentiation induced by retinoic acid (RA). We found that laminin-511 but not -521 accumulates in the committed cells during early steps of hESC differentiation. We also performed a comprehensive analysis of the laminin chain repertoire and found that pluripotent hESC express a more diverse range of laminin chains than shown previously. In particular, we provide the evidence that in addition to α1, α5, β1, β2 and γ1 chains, hESC express α2, α3, β3, γ2 and γ3 chain proteins and mRNA. Additionally, we found that a variant of laminin α3 chain—145 kDa—accumulated in RA-treated hESC showing that these cells produce prevalently specifically modified version of α3 chain in early phase of differentiation.     

Vascular plant and bryophytes species representation in the protected areas network on the national scale

The complexity of nature conservation raises questions about biodiversity protection at the level of species as well as their spatial distribution between differently designated nature conservation areas. We have concentrated on comparison of the existing protected areas and recently established conservation initiative areas—Important Plant Areas. We have estimated how well these areas support the protection of two plant groups—bryophytes and vascular plants. We sought answers to the following questions: (a) are there any trends in the distribution of protected bryophyte and vascular plant species in the protected areas network, and (b) does the Important Plant Areas network promote better protection of bryophyte species compared with the existing protected areas network. Our results demonstrated that bryophytes need special care in nature conservation decisions to reach the reasonable conservation target. Important Plant Areas that were targeted to vascular plants have less importance in preserving bryophyte diversity than already existing conservation areas system. Conservation programs like IBA, IPA etc. have their specific tool and outcome to add conservation values to the existing protected areas system.