Decorin

Ehlers-Danlos Syndrome (EDS) represents a cluster of specific genetic connective tissue disorders. It is clinically evoked when skin appears velvety and hyperextensible, in combination with joint laxity and connective tissue fragility. The hypermobile variant (EDSH) is among the most common presentations. It presents as an autosomal dominant pathology. The genetic mutation presently remains undisclosed in most cases. However, ultrastructural alterations are often distinguishable. Ehlers-Danlos Syndrome Hypermobile (EDSH) is mostly observed in women in whom additional signs to joint laxity are present. Hyperextensibility and/or velvety presentation of skin is one of the two major diagnostic signs in EDSH. Atrophic scars and delayed wound healing are commonly present. These features have to be considered
in particular by plastic surgeons. The ultrastructural skin changes show various numbers of flower-like collagen fibres as well as other abnormalities in the connective tissue components.

BACKGROUND: Decorin, a leucine-rich proteoglycan that is produced by decidual cells, limits invasion and endovascular differentiation of extravillous trophoblast cells during early placentation by binding to multiple tyrosine kinase receptors, in particular, vascular endothelial growth factor receptor-2. OBJECTIVE: Because many studies have reported an association between poor trophoblast invasion and endovascular differentiation with preeclampsia, the studies reported here tested (1) whether decorin over-expression in the chorionic villi and/or basal decidua is associated with preeclampsia and, if so, (2) whether this association results in a hypoinvasive placenta, and (3) whether elevated plasma decorin concentration in the second trimester is a predictive biomarker for preeclampsia. STUDY DESIGN: Decorin messenger RNA expression was measured with quantitative polymerase chain reaction at the tissue level and with in situ hybridization at the cellular level using 35 S-labeled antisense com-plimentary RNA probe in placentas from healthy control subjects and subjects with preeclampsia (14 each, 23-40 weeks of gestation). Tissue sections of the same placentas were also immunostained for decorin protein. A decorin over-expressing human endometrial stromal cell line was tested for invasion-regulatory effects on an invasive first-trimester extravillous trophoblast cell line HTR-8/SVneo plated in cocultures that were separated by a semipermeable membrane. Furthermore, we conducted retrospective measurements of plasma decorin levels during the second trimester (15-18 weeks of gestation) in a cohort of 28 body mass indexematched pairs of control subjects and subjects with preeclampsia before the onset of clinical disease. RESULTS: First, decorin messenger RNA expression at the cellular level measured with in situ hybridization exhibited profoundly higher expression levels in basal plate decidual cells within the placentas from preeclamptic

Numerous stimulatory growth factors that can influence muscle regeneration are known. Recently, it has been demonstrated that neutralization of muscle growth inhibitory factors, such as myostatin (Mstn; also known as growth differentiation factor 8, Gdf8), also leads to increased muscle regeneration in mdx mice that are known to have cycles of degeneration. However, the precise mechanism by which Mstn regulates muscle regeneration has not yet been fully determined. To investigate the role of Mstn in adult skeletal muscle regeneration, wild-type and myostatin-null (Mstn-/-) mice were injured with notexin. Forty-eight hours after injury, accelerated migration and enhanced accretion of myogenic cells (MyoD1+) and macrophages (Mac-1+) was observed at the site of regeneration in Mstn-/- muscle as compared with wild-type muscle. Inflammatory cell numbers decreased more rapidly in the Mstn-/- muscle, indicating that the whole process of inflammatory cell response is accelerated in Mstn-/- mice. Consistent with this result, the addition of recombinant Mstn reduced the activation of satellite cells (SCs) and chemotactic movements of both myoblasts and macrophages ex vivo. Examination of regenerated muscle (28 days after injury) also revealed that Mstn-/- mice showed increased expression of decorin mRNA, reduced fibrosis and improved healing as compared with wild-type mice. On the basis of these results, we propose that Mstn negatively regulates muscle regeneration not only by controlling SC activation but also by regulating the migration of myoblasts and macrophages to the site of injury. Thus, antagonists of Mstn could potentially be useful as pharmacological agents for the treatment of disorders of overt degeneration and regeneration.

Background  Transforming growth factor (TGF-β1) is postulated to play an important role in maintaining the structure and function of arterial tissue and protection against development of arteriosclerosis. The TGF-β1-induced production of a stable extra-cellular matrix-rich plaque phenotype is suggested to be part of the protection against a switch to an unstable rupture-prone arteriosclerotic plaque.Materials and methods  This study addresses the question of whether the expression profile and the type of extra-cellular matrix (ECM) generated by TGF-β1 stimulation have the structural feature of a fibril-rich stable matrix. Seventeen genes codings for ECM components of human coronary smooth muscle cells (SMCs) after a 24-h stimulation by TGF-β1 have been analyzed.Results  Real-time RT-PCR was used to quantify the mRNA of genes under investigation. It was found that after TGF-β1 stimulation (a) the up-regulation of COL1A1-specific mRNA was associated with increased [3H]proline incorporation into the α-1 and -2 chains of collagen type I, (b) the up-regulation of biglycan- and syndecan-1-specific mRNA corresponded to an increased [35S]sulphate and [4,5-3H]leucine incorporation into the biglycan molecule and to an increase of syndecan-1 protein, (c) the up-regulated FGF-2 gene accounted predominantly for the ECM-bound subfraction of FGF-2-protein and (d) fibronectin and thrombospondin exhibited a significantly higher mRNA level. In contrast collagen XIV, a minor collagen type, and the proteoglycan decorin were down-regulated. The down-regulated decorin changed its structure by elongation and reduced GlcA to IdoA epimerization of the dermatan sulphate side-chain as judged by [35S]sulphate metabolic labelling experiments. No significant changes in response to TGF-β1 were observed for the collagen types III, VI and XVI, for versican, perlecan and the syndecans-2 and -4.Conclusions  It was concluded from the data that the TGF-β1-induced formation of a highly specific multicomponent extra-cellular matrix on coronary arterial SMCs could provide in vivo mechanical strength to the neointima in arteriosclerotic lesions and to the fibrous cap overlying the lipid core.

The microanatomic distribution of several noncollagenous proteins (NCPs) in bone matrix was examined by immunohistochemical analysis of glycol-methyl methacrylate-embedded normal adult human bone biopsies. Osteopontin and bone sialoprotein stained throughout the lamellae of both trabecular and cortical bone. Cement lines (cortical and trabecular) and the mineralized matrix immediately adjacent to each Haversian canal were intensely stained. Osteocalcin was detected in cement lines; however, lamellar staining varied depending on the location within the individual unit of bone. In cortical bone, the inner concentric lamellae of osteons were often unstained but the outer lamellae were heavily stained for osteocalcin. Osteonectin was not detected in cement lines and in most specimens revealed a pattern similar to that of osteocalcin with respect to the absence of immunostaining within the inner concentric lamellae. Decorin was prominent in the perilacunar matrix, the canaliculi of osteocytes, and the matrix immediately adjacent to quiescent Haversian canals. Biglycan appeared evenly distributed throughout cortical and trabecular bone matrix. These results suggest that the incorporation of NCPs into matrix may vary depending on the stage of formation of individual bone units. The specific distribution and spatial relationship of these NCPs may be related to the function of each protein during bone resorption and formation. The distinct patterns of NCP localization in bone support the hypothesis that in addition to their structural and mineral-inducing properties, these proteins may influence the events associated with bone remodeling, such as recruitment, attachment, differentiation, and activity of bone cells.

Analysis of the N-terminal sequence of decorin purified from connective tissues and comparison with the sequence deduced from the cDNA indicate that the nascent proteoglycan has a 14 amino acid residue N-terminal propeptide. Mammalian expression vectors encoding wild-type decorin and decorin with deletions in the propeptide were used to transform COS and CHO cells. Cells transformed with vectors encoding deletion

Previously, the authors demonstrated that the lack of the P2X(7) receptor impairs epithelial wound healing and stromal collagen organization in the cornea. The goal here is to characterize specific effects of the P2X(7) receptor on components of the corneal stroma extracellular matrix. Unwounded corneas from P2X(7) knockout mice (P2X(7) (-/-)) and C57BL/6J wild type mice (WT) were fixed and prepared for quantitative and qualitative analysis of protein expression and localization using Real Time PCR and immunohistochemistry. Corneas were stained also with Cuprolinic blue for electron microscopy to quantify proteoglycan sulfation in the stroma. P2X(7) (-/-) mice showed decreased mRNA expression in the major components of the corneal stroma: collagen types I and V and small leucine-rich proteoglycans decorin, keratocan, and lumican. In contrast P2X(7) (-/-) mice showed increased mRNA expression in lysyl oxidase and biglycan. Additionally, we observed increases in syndecan 1, perlecan, ...