Fibronectin Gene Expression Research Articles

Biochemical basis of vocal fold mobilization after microflap surgery in a rabbit model

To investigate phonation-related extracellular matrix (ECM) changes in the vocal fold lamina propria after microflap surgery using an in vivo rabbit phonation model. Prospective animal study. Twenty-four New Zealand White rabbits were used in this study. Quantitative polymerase chain reaction and immunohistochemistry were used to investigate alterations in vocal fold ECM proinflammatory and profibrotic gene, and protein expression from a control group of animals receiving a microflap without phonation and a separate group of animals receiving experimentally induced phonation on postmicroflap days 0, 3, and 7. IHC demonstrated the highest concentration of CD45 in vocal folds on postoperative day 0. Staining for CD45 was absent by postoperative day 7, with no differences in CD45 staining between groups. Fibronectin gene expression increased significantly on postoperative day 3 in the control and experimentally induced phonation groups, with maximal staining of fibronectin around the microflap incision on postoperative day 7. No alterations in cyclooxygenase-2, interleukin-1β, and transforming growth factor-β1 gene expression were observed between groups. Results of the present study revealed an acute inflammatory response in the vocal fold at the time of microflap (day 0) and up to 3 days post-microflap. By post-operative day 3, staining of CD45 positive cells decreased, with essentially no evidence of inflammation by post-operative day 7. With the end of the acute inflammatory response occurring around day 3, these data may provide support for mobilizing tissue after inflammation has subsided and the process of active tissue remodeling has ensued (days 3-7). N/A.

Epilobium angustifolium extract demonstrates multiple effects on dermal fibroblasts in vitro and skin photo-protection in vivo

Stress-induced fibroblast senescence is thought to contribute to skin aging. Ultraviolet light (UV) radiation is the most potent environmental risk factor in these processes. An Epilobium angustifolium (EA) extract was evaluated for its capacity to reverse the senescent response of normal human dermal fibroblasts (NHDF) in vitro and to exhibit skin photo-protection in vivo. The HPLC-UV-MS analysis of the EA preparation identified three major polyphenol groups: tannins (oenothein B), phenolic acids (gallic and chlorogenic acids) and flavonoids. EA extract increased the cell viability of senescent NHDF induced by serum deprivation. It diminished connective tissue growth factor and fibronectin gene expressions in senescent NHDF. Down-regulation of the UV-induced release of both matrix metalloproteinase-1 and -3 and the tissue inhibitor of matrix metalloproteinases-1 and -2, and also down-regulation of the gene expression of hyaluronidase 2 were observed in repeatedly UV-irradiated NHDF after EA extract treatment. Interestingly, EA extract diminished the down-regulation of sirtuin 1 dampened by UV-irradiation. The application of EA extract using a sub-irritating dose protected skin against UV-induced erythema formation in vivo. In summary, EA extract diminished stress-induced effects on NHDF, particularly on connective tissue growth factor, fibronectin and matrix metalloproteinases. These results collectively suggest that EA extract may possess anti-aging properties and that the EA polyphenols might account for these benefits.

ASSA13-03-38 Selenium Ameliorate Myocardial Fibrosis in Diabetic Rats Through Inhibiting GPx- ROS-Smad- CTGF Signalling Pathway

ObjectiveIt has been mentioned that myocardial fibrosis which contributes to cardiac dysfunctions is one of the hall markers of diabetic cardiomyopathy. Up-regulation of reactive oxidative species (ROS)/TGF- beta 1/Smad signalling...

Anti‐fibrosis effect of BMP‐7 peptide functionalization on cobalt chromium alloy

Orthopedic metallic prosthetic implants are commonly made of cobalt chromium (CoCr) alloys. However, such metal-based implants are susceptible to fibrous capsule formation on the implant surface after implantation. At the bone-implant interface, this capsule can prevent implant integration, resulting in loosening and failure. Minimizing the development of such a capsule on the CoCr surface would improve direct bone-implant bonding leading to long-term implant functionality. We evaluated the anti-fibrosis effect of bone morphogenic protein-7 (BMP-7) peptide covalently bonded to CoCr alloy. This peptide, a biomimetic derivation of the knuckle epitope of BMP-7, was conjugated at the N-terminus with a cysteine amino acid. X-ray photoelectron spectroscopy (XPS) and probe binding assay were used to evaluate different stages of grafting and surface functionalization using polydopamine coating. Cellular functions were studied using fibroblast attachment, cell proliferation, and MTT assays. Fibroblasts were grown on functionalized and pristine CoCr substrates, and the efficacy of BMP-7 peptide on anti-fibrosis was analyzed via gene expression and protein expression of fibrosis markers ACTA2, Collagen 1A1, and fibronectin. The peptide functionalized substrates showed significant reduction of fibrosis markers expression after 1 week of incubation compared to controls. BMP-7 signaling pathway activation was shown by the presence of phosphorylation of Smad1/5/8. These findings may contribute to the improvement of CoCr implants in orthopedic surgery applications.

Inhibition of RhoA/Rho-kinase pathway suppresses the expression of extracellular matrix induced by CTGF or TGF-β in ARPE-19.

To investigate the role of Rho-associated protein kinase (ROCK) inhibitor, Y27632, in mediating the production of extracellular matrix (ECM) components including fibronectin, matrix metallo-proteinase-2 (MMP-2) and type I collagen as induced by connective tissue growth factor (CTGF) or transforming growth factor-β (TGF-β) in a human retinal pigment epithelial cell line, ARPE-19. The effect of Y27632 on the CTGF or TGF-β induced phenotype in ARPE-19 cells was measured with immunocytochemistry as the change in F-actin. ARPE-19 cells were treated with CTGF (1, 10, 100ng/mL) and TGF-β (10ng/mL) in serum free media, and analyzed for fibronectin, laminin, and MMP-2 and type I collagen by RT-qPCR and immunocytochemistry. Cells were also pretreated with an ROCK inhibitor, Y27632, to analyze the signaling contributing to ECM production. Treatment of ARPE-19 cells in culture with TGF-β or CTGF induced an ECM change from a cobblestone morphology to a more elongated swirl pattern indicating a mesenchymal phenotype. RT-qPCR analysis and different gene expression analysis demonstrated an upregulation in expression of genes associated with cytoskeletal structure and motility. CTGF or TGF-β significantly increased expression of fibronectin mRNA (P=0.006, P=0.003 respectively), laminin mRNA (P=0.006, P=0.005), MMP-2 mRNA (P= 0.006, P= 0.001), COL1A1 mRNA (P=0.001, P=0.001), COL1A2 mRNA (P=0.001, P=0.001). Preincubation of ARPE-19 with Y27632 (10mmol/L) significantly prevented CTGF or TGF- β induced fibronectin (P=0.005, P=0.003 respectively), MMP-2 (P= 0.003, P=0.002), COL1A1 (P=0.006, P=0.003), and COL1A2 (P=0.006, P=0.004) gene expression, but not laminin (P=0.375, P=0.516). Our study demonstrated that both TGF-β and CTGF upregulate the expression of ECM components including fibronectin, laminin, MMP-2 and type I collagen by activating the RhoA/ROCK signaling pathway. During this process, ARPE-19 cells were shown to change from an epithelial to a mesenchymal phenotype in vitro. Y27632, a ROCK inhibitor, inhibited the transcription of fibronectin, MMP-2 and type I collagen, but not laminin. The data from our work suggest a role for CTGF as a profibrotic mediator. Inhibiting the RhoA/ROCK pathway represents a potential target to prevent the fibrosis of RPE cells. This might lead to a novel therapeutic approach to preventing the onset of early PVR.

Effect of a single subacromial prednisolone injection in acute rotator cuff tears in a rat model

This study examined the early effect of a subacromial steroid injection on injured rotator cuff tendon. Forty rats were allocated into two groups: a steroid injection (group 1) and no injection as control (group 2). A full-thickness defect was made at the unilateral infraspinatus tendon in both groups. A single dose of methylprednisolone was injected in steroid group. The tendon was harvested at 1, 3, 7, 14, and 42 days after surgery; gene expression and immunohistochemical study were performed for type-I/III collagen, tumour necrosis factor (TNF)-α, and extracellular matrix molecules. The type-III to type-I collagen ratio was at 7 days higher in the steroid group than that in the control group and decreased to the control level at 14 days and was maintained until 42 days. The general expression of the MMPs and TIMPs between two groups showed similar pattern regardless of the steroid injection. The gene expression of aggrecan and fibronectin in the steroid group was significantly higher than that in the control group (p < 0.05) at 3 days after surgery. They decreased to the equal level with control group at 7 days after surgery. Both groups showed no significant difference between aggrecan and fibronectin until 42 days after surgery (n.s.). A subacromial steroid injection may alter the collagen composition and extracellular matrix and interfere with the healing process in an acute tear of rat infraspinatus tendon at the early phase after the injection. However, these alterations seem to become normalized after the early inflammatory healing phase.

Fibronectin Gene Expression in Human Adipose Tissue and Its Associations with Obesity-Related Genes and Metabolic Parameters

Limited data are available on the in vivo expression of fibronectin, one of the main extracellular matrix components. We investigated the expression of fibronectin in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) and the associations of leptin, adiponectin, and vaspin gene expression with metabolic parameters in obese women. We recruited female subjects undergoing bariatric surgery for obesity (n = 24) and patients undergoing benign gynecological surgery as the control group (n = 23). We measured anthropometric variables, abdominal fat distribution, metabolic parameters, serum concentrations of leptin, adiponectin, and vaspin, and depot-specific mRNA expression of fibronectin, leptin, adiponectin, and vaspin. Fibronectin expression in both VAT and SAT was significantly lower in the obese group than in the control group. Fibronectin expression in both VAT and SAT were negatively correlated with body mass index or waist circumference, with higher prominence in VAT. In multiple regression analysis, fibronectin expression in both VAT and SAT was negatively correlated with serum leptin concentration. Fibronectin expression in VAT was negatively correlated with leptin expression in VAT. Additionally, fibronectin expression in SAT was negatively correlated with leptin expression in SAT and positively correlated with adiponectin expression in VAT and SAT. We found significant negative associations between depot-specific fibronectin expression in human adipose tissue and obesity indices and obesity-related biomarkers. Our results suggest that fibronectin expression may contribute to obesity and metabolic dysregulation in humans.

Evaluating the performance of fibronectin 1 (FN1), integrin α4β1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 as the potential biomarkers of oral squamous cell carcinoma (OSCC)

Objectives: Some extracellular matrix genes as prognostic biomarkers for oral squamous cell carcinoma (OSCC) were evaluated.Methods: We investigated gene expression of fibronectin 1 (FN1), integrin α4β1 (ITGA4), syndecan-2 (SDC2), and glycoprotein CD44 in matched OSCC/margin tissues.Results: Areas under receiver-operating characteristic curves (AUCs) of relative mRNA expression of FN1, ITGA4, SDC2, and CD44 were 0.700, 0.677, 0.513, and 0.549, respectively. For tongue/mouth floor and edentulous ridge, AUC for FN1 and ITGA4 were 0.827 and 0.725 and sensitivities/specificities were 80%/84% and 88%/52%, respectively.Conclusion: FN1 and ITGA4 are potential OSCC biomarkers for tongue/mouth floor and edentulous ridge.

Expression of Tax-interacting protein 1 (TIP-1) facilitates angiogenesis and tumor formation of human glioblastoma cells in nude mice

Glioblastoma is the most common and fatal type of primary brain tumors featured with hyperplastic blood vessels. Here, we performed meta-analyses of published data and established a correlation between high TIP-1 expression levels and the poor prognosis of glioblastoma patients. Next, we explored the biological relevance of TIP-1 expression in the pathogenesis of glioblastoma. By using orthotopic and heterotopic mouse models of human glioblastomas, this study has characterized TIP-1 as one contributing factor to the tumor-driven angiogenesis. In vitro and in vivo functional assays, along with biochemical analyses with microarrays and antibody arrays, have demonstrated that TIP-1 utilizes multiple pathways including modulating fibronectin gene expression and uPA protein secretion, to establish or maintain a pro-angiogenic microenvironment within human glioblastoma. In conclusion, this work supports one hypothesis that TIP-1 represents a novel prognostic biomarker and a therapeutic target of human glioblastoma.

Early and Delayed Tranilast Treatment Reduces Pathological Fibrosis Following Myocardial Infarction

Tranilast has been shown to inhibit TGFβ1-related fibrosis and organ failure in various disease models. We sought to examine the effects of tranilast on left ventricular (LV) remodelling post-MI. Following coronary artery ligation, Sprague Dawley rats were randomised to receive tranilast (300mg/kg/d, p.o.) or vehicle control over one of two treatment periods: (1) from 24h until seven days post-MI, (2) from seven days to 28 days post-MI. Cardiac tissue was harvested for molecular, immunohistochemical and cell culture analyses. Tranilast treatment of MI rats from 24h until seven days post-MI reduced myocardial collagen content, α1 (I) procollagen, TGFβ1 and CTGF mRNA transcripts, monocyte/macrophage infiltration and exacerbated infarct expansion compared with vehicle-treatment. Delaying the commencement of tranilast treatment to seven days post-MI attenuated myocardial fibrosis, gene expression of α1(I) procollagen, α1(III) procollagen, fibronectin, TGFβ1 and CTGF mRNA transcripts, and monocyte/macrophage infiltration at 28d compared to vehicle-treatment, without detriment to infarct healing. Extended post-MI also preserved LV infarct size. In cultures of rat cardiac fibroblasts, tranilast attenuated TGFβ1-stimulated fibrogenesis. Tranilast inhibits myocardial TGFβ1 expression, fibrosis in rat post-MI and collagen production in cardiac fibroblasts. While tranilast intervention from 24h post-MI exacerbated infarct expansion, delaying the commencement of treatment to seven days post-MI impeded LV remodelling.

Fibronectin expression is decreased in metastatic renal cell carcinoma following endostatin gene therapy

Tumor cells induce the disruption of homeostasis between cellular and extracellular compartments to favor tumor progression. The expression of fibronectin (FN), a matrix glycoprotein, is increased in several carcinoma cell types, including renal cell carcinoma (RCC). RCC are highly vascularized tumors and are often amenable to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the modulation of FN gene expression by ES gene therapy in a murine metastatic renal cell carcinoma (mRCC) model. Balb/C mice bearing Renca cells were treated with NIH/3T3-LXSN cells or NIH/3T3-LendSN cells. At the end of the experiment, the ES serum levels were measured, and the FN gene expression was assessed using real-time PCR. The tissue FN was evaluated by western blotting and by immunofluorescence analysis. The ES serum levels in treated mice were higher than those in the control group (P<0.05). ES treatment led to significant decreases at the FN mRNA (P<0.001) and protein levels (P<0.01). Here, we demonstrate the ES antitumor effect that is mediated by down-regulation of FN expression in mRCC.

Ginseng Reverses Established Cardiomyocyte Hypertrophy and Postmyocardial Infarction-Induced Hypertrophy and Heart Failure

A major challenge in the treatment of heart failure is the ability to reverse already-established myocardial remodeling and ventricular dysfunction, with few available pharmacological agents prescribed for the management of heart failure having demonstrated successful reversal of the remodeling and hypertrophic processes. North American ginseng (Panax quinquefolius) has previously been shown to effectively prevent cardiomyocyte hypertrophy and heart failure. Here, we determined whether North American ginseng can reverse established cardiomyocyte hypertrophy in cultured myocytes as well as hypertrophy and left ventricular dysfunction in experimental heart failure secondary to coronary artery occlusion. Ginseng was administered in drinking water (0.9 g/L) ad libitum to rats after 4 weeks of sustained coronary artery ligation when heart failure was established or to angiotensin II- (100 nmol/L), endothelin-1- (10 nmol/L), or phenylephrine- (10 µmol/L) induced hypertrophic cultured neonatal ventricular cardiomyocytes. Echocardiographic and catheter-based measurements of hemodynamic parameters 4 weeks after starting ginseng treatment (8 weeks postinfarction) revealed nearly complete reversibility of systolic and diastolic abnormalities. Similarly, ginseng administration to hypertrophic cardiomyocytes resulted in a complete reversal to a normal phenotype after 24 hours as determined by cell surface area and expression of molecular markers. The effects of ginseng both in vivo and in cultured cardiomyocytes were associated with reversal of calcineurin activation and reduced nuclear translocation of the transcription factor NFAT3 (nuclear factor of activated T cells 3) in cultured myocytes. Moreover, the beneficial effect of ginseng was associated with normalization in the gene expression of profibrotic markers, including collagen (I and III) and fibronectin. This study demonstrates a marked ability of ginseng to reverse cardiac hypertrophy, myocardial remodeling, and heart failure, which was associated with and likely mediated by reversal of calcineurin activation. Ginseng may offer a potentially effective approach to reverse the myocardial remodeling and heart failure processes, particularly in combination with other treatment modalities.

Abstract 2413: Human glypican-3 promotes hepatocellular carcinoma progression via induction of epithelial-mesenchymal transition

Abstract Hepatocellular carcinoma (HCC) is the third most important cause of cancer mortality worldwide. Epithelial-mesenchymal transition (EMT) has been shown to be an important biological process involved in the development and progression of HCC. The factors driving this process, however, are still largely unclear. Glypican-3 (GPC3) is upregulated in HCC and this is associated with poor prognosis. The details of the biological role of GPC3 in HCC are, however, yet to be fully elucidated. We hypothesized that GPC3 may promote HCC progression by inducing EMT. In this study we have examined the effect of human GPC3 in the progression of HCC using a murine HCC cell line (1MEA) derived from Balb/c mouse. We observed that the 1MEA cell line does not express GPC3 and we stably transfected human GPC3 into this cell line. 1MEA cells stably transfected with human glypican-3 (1MEAhGPC3) were then transplanted subcutaneously into 8 Balb/c mice. In comparison, wild type 1MEA was also transplanted into 8 separate Balb/c mice. Further, we performed a comparative analysis of the gene expression of E-cadherin, vimentin, collagen I, fibronectin, twist, slug and snail in both wild type 1MEA and 1MEAhGPC3. 18 days post-transplantation, tumor volume was analyzed. 5 mice transplanted with wild type 1MEA had not yet developed tumors whereas 3 mice transplanted with 1MEAhGPC3 developed tumors that had grown past the allowed tumor volume for the protocol and were sacrificed. Analysis of the remaining mice (3 transplanted with 1MEA and 5 with 1MEAhGPC3 revealed that tumors from 1MEA were 8-fold more voluminous than tumors from 1MEAhGPC3. Comparative analysis of the gene expression profile of 1MEA versus 1MEAhGPC3 revealed that transfection with hGPC3 had resulted in increased expression of mesenchymal markers (collagen I by 27.5-fold, fibronectin by 18-fold, vimentin by 3-fold), loss of epithelial marker (E-cadherin loss by 99%) and increased expression of transcriptional regulators of EMT (twist by 11.7-fold, slug by 148-fold and snail by 8.7-fold).These data clearly show that hGPC3 promotes HCC progression by inducing EMT in HCC cells. To our knowledge, this is the first experimental evidence that hGPC3's role in HCC is associated with induction of EMT and it suggests that therapeutic targeting of GPC3 in human HCC may be an effective approach to the treatment of advanced HCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2413. doi:1538-7445.AM2012-2413

Dermatan sulphate in methoxy polyethylene glycol-polylactide-co-glycolic acid scaffolds upregulates fibronectin gene expression but has no effect on in vivo osteochondral repair

The purpose of the study was to investigate the effect of dermatan sulphate (DS) addition to biodegradable methoxy polyethylene glycol (MPEG) substituted polylactide-co-glycolic acid (PLGA) scaffolds for cartilage repair in vitro and in vivo. Human chondrocytes from eight patients undergoing anterior cruciate ligament reconstruction were isolated and cultured in 5% oxygen on MPEG-PLGA scaffolds±DS for one, three, seven and 14 days. Analyses were performed using quantitative gene expression analysis for chondrogenic and cell attachment markers. An osteochondral drill hole defect was created in the intertrochlear groove of the distal femur in 20 New Zealand white rabbits (defects n=20). When bleeding was observed, the defects were treated with MPEG-PLGA scaffolds±DS. Twelve weeks after surgery the rabbits were sacrificed and the defects were analysed using histological grading with O'Driscoll scoring. DS addition to MPEG-PLGA scaffolds resulted in a significant upregulation of fibronectin gene expression on day 1. No differences were observed in chondrogenic gene expression. There were no differences between the two groups in histological grading (+DS 10.3 and -DS 9.6). Upregulation of fibronectin in vitro indicating early cell-scaffold interaction and attachment did not result in improved cartilage repair in an osteochondral defect model in rabbits.

Transforming Growth Factor–β Evokes Ca2+ Waves and Enhances Gene Expression in Human Pulmonary Fibroblasts

Fibroblasts maintain the structural framework of animal tissue by synthesizing extracellular matrix molecules. Chronic lung diseases are characterized in part by changes in fibroblast numbers, properties, and more. Fibroblasts respond to a variety of growth factors, cytokines, and proinflammatory mediators. However, the signaling mechanisms behind these responses have not been fully explored. We sought to determine the role of Ca(2+) waves in transforming growth factor-β (TGF-β)-mediated gene expression in human pulmonary fibroblasts. Primary human pulmonary fibroblasts were cultured and treated with TGF-β and different blockers under various conditions. Cells were then loaded with the Ca(2+) indicator dye Oregon green, and Ca(2+) waves were monitored by confocal [Ca(2+)](i) fluorimetry. Real-time PCR was used to probe gene expression. TGF-β (1 nM) evoked recurring Ca(2+) waves. A 30-minute pretreatment of SD 208, a TGF-β receptor-1 kinase inhibitor, prevented Ca(2+) waves from being evoked by TGF-β. The removal of external Ca(2+) completely occluded TGF-β-evoked Ca(2+) waves. Cyclopiazonic acid, an inhibitor of the internal Ca(2+) pump, evoked a relatively slowly developing rise in Ca(2+) waves compared with the rapid changes evoked by TGF-β, but the baseline fluorescence was increased. Ryanodine (10(-5) M) also blocked TGF-β-mediated Ca(2+) wave activity. Real-time PCR showed that TGF-β rapidly and dramatically increased the gene expression of collagen A1 and fibronectin. This increase was blocked by ryanodine treatment and cyclopiazonic acid. We conclude that, in human pulmonary fibroblasts, TGF-β acts on ryanodine-sensitive channels, leading to Ca(2+) wave activity, which in turn amplifies extracellular matrix gene expression.

Inhibiting MicroRNA-192 Ameliorates Renal Fibrosis in Diabetic Nephropathy

TGF-β1 upregulates microRNA-192 (miR-192) in cultured glomerular mesangial cells and in glomeruli from diabetic mice. miR-192 not only increases collagen expression by targeting the E-box repressors Zeb1/2 but also modulates other renal miRNAs, suggesting that it may be a therapeutic target for diabetic nephropathy. We evaluated the efficacy of a locked nucleic acid (LNA)-modified inhibitor of miR-192, designated LNA-anti-miR-192, in mouse models of diabetic nephropathy. LNA-anti-miR-192 significantly reduced levels of miR-192, but not miR-194, in kidneys of both normal and streptozotocin-induced diabetic mice. In the kidneys of diabetic mice, inhibition of miR-192 significantly increased Zeb1/2 and decreased gene expression of collagen, TGF-β, and fibronectin; immunostaining confirmed the downregulation of these mediators of renal fibrosis. Furthermore, LNA-anti-miR-192 attenuated proteinuria in these diabetic mice. In summary, the specific reduction of renal miR-192 decreases renal fibrosis and improves proteinuria, lending support for the possibility of an anti-miRNA-based translational approach to the treatment of diabetic nephropathy.

LLLT In Vitro Effects on the Proliferation of Human Gingival Fibroblasts and on the Gene Expression of Fibronectin and Type I Collagen

LLLT In Vitro Effects on the Proliferation of Human Gingival Fibroblasts and on the Gene Expression of Fibronectin and Type I Collagen

Encephalotrigeminal Angiomatosis (Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome): A Review.

Sturge-Weber syndrome (SWS) (encephalotrigeminal angiomatosis) is a phakomatosis associated with port-wine stains of the face, seizures, mental retardation, and usually ipsilateral meningeal vascular malformations. The classic form affects leptomeninges, eyes, and face. Although the precise etiology and pathogenesis are unclear, the postulated defect is primary venous dysplasia with failure of the primordial embryonic venous plexus to regress. A spontaneous somatic mutation in fibroblast fibronectin gene expression in the vascular malformation may occur during embryonic development. Ocular involvement is characterized by conjunctival, episcleral, retinal, and choroidal vascular abnormalities. The vascular lesions have been inconsistently described as angiomas, hemangiomas, and vascular malformations. Based on the endothelial cellular activity, they can be considered vascular malformations (or port-wine stains), which never regress spontaneously. Congenital, developmental, and adult-onset glaucoma are often seen when the malformations involve the distribution of the first branch of the trigeminal nerve.Both mechanical and vascular causes have been proposed to account for the development of glaucoma. The mechanical theory is based on obstruction of aqueous outflow secondary to developmental anterior chamber angle abnormalities, and the vascular theory is based primarily on elevated episcleral venous pressure. Management of glaucoma in patients with SWS is often challenging and is aimed at controlling intraocular pressure and preventing progressive visual loss and blindness. It also carries an increased risk for surgical complications. This review summarizes the literature regarding the genetics, clinical features, and management of ocular complications of SWS with special focus on glaucoma.

Effects of decorin and biglycan on human airway smooth muscle cell adhesion

Growth on a decorin matrix results in decreased human airway smooth muscle cell (HASMC) number, by decreasing proliferation and increasing apoptosis. We questioned whether these effects were related to abnormal extracellular matrix (ECM)-cell adhesion. HASMCs were seeded on decorin, biglycan, collagen type I or plastic. Actin organization and focal adhesion formation were assessed by staining for filamentous (F) and globular (G) actin, and vinculin, respectively. Gene expression for focal adhesion proteins, ECM molecules and HASMC receptors was measured. Protein levels for fibronectin, α2, α5, αv and β3 integrin subunits and, focal adhesion kinase (FAK) were assessed. F-actin filaments were prominent in cells seeded on collagen I and plastic, less apparent in cells cultured on biglycan and faint in cells on decorin. Vinculin clustering was decreased in cells seeded on decorin and biglycan, as was vinculin gene expression. Compared to cells on plastic, cells on decorin had an increase in fibronectin gene expression. Seeding on decorin caused an increase in α2 integrin subunit and platelet-derived growth factor receptor A gene expression. There was also an increase in α2 and αv integrin subunit protein. Finally, FAK protein levels in cells seeded on decorin or biglycan were decreased compared to cells seeded on plastic or collagen I. Cells grown on proteoglycan matrices demonstrate evidence of abnormalities during many of the key processes involved in normal cell adhesion. Upregulation of cell surface receptor proteins, such as α2 integrin subunit, may represent a compensatory mechanism to overcome poor adhesion induced by growth on these matrices.

TFCP2c/LSF/LBP-1c is required for Snail1-induced fibronectin gene expression

Fibronectins are cell-secreted glycoproteins that modulate cell attachment, spreading, migration, morphology, differentiation and oncogenic transformation. Fibronectin expression is activated during EMT (epithelial-mesenchymal transition) and is a hallmark of mesenchymal cells. It is shown in the present study that a transcription factor previously unrelated with EMT, TFCP2c/LSF/LBP-1c, was translocated to the nucleus and bound to the fibronectin promoter upon EMT induction by Snail1. Consequently, the interference of TFCP2c/LSF/LBP-1c's activity prevented fibronectin expression. Moreover, TFCP2c/LSF/LBP-1c was detected in nuclei of embryonic dermal mesenchymal cells adjacent to the hair bud, a cell population that expresses endogenous nuclear Snail1 and fibronectin. Therefore we indicate a new molecular role for TFCP2c/LSF/LBP-1c in fibronectin expression.