V3: an enigmatic isoform of the proteoglycan versican.

V3 is an isoform of the extracellular matrix (ECM) proteoglycan (PG) versican generated through alternative splicing of the versican gene such that the two major exons coding for sequences in the protein core that support chondroitin sulfate (CS) glycosaminoglycan (GAG) chain attachment are excluded. Thus, versican V3 isoform carries no GAGs. A survey of PubMed reveals only 50 publications specifically on V3 versican, so it is a very understudied member of the versican family, partly because to date there are no antibodies that can distinguish V3 from the CS-carrying isoforms of versican, that is, to facilitate functional and mechanistic studies.

The synthesis and secretion of versican isoform V3 by mammalian cells: A role for N-linked glycosylation.

Versican is a large extracellular matrix (ECM) chondroitin sulfate (CS) proteoglycan found in most soft tissues, which is encoded by the VCAN gene. At least four major isoforms (V0, V1, V2, and V3) are generated via alternative splicing. The isoforms of versican are expressed and accumulate in various tissues during development and disease, where they contribute to ECM structure, cell growth and migration, and immune regulation, among their many functions.

Measuring patient-centredness in publicly funded fertility care: A New Zealand validation and international comparison of the Patient-Centred Questionnaire-Infertility.

Background: The Patient-Centred Questionnaire-Infertility (PCQ-Infertility) has proven to be a reliable instrument to assess the extent of patient-centredness of fertility care in European countries.

Aims: To validate the PCQ-Infertility in New Zealand (NZ) and to compare results with international experience.

Materials And Methods: A cross-sectional 46-item questionnaire study among 409 women undergoing publicly funded fertility care (intrauterine insemination or in vitro fertilisation / intracytoplasmic sperm injection) in three fertility clinics in the Northern Auckland region was performed between October 2015 and September 2016.

Immune Checkpoint Ligand PD-L1 Is Upregulated in Pulmonary Lymphangioleiomyomatosis.

Pulmonary lymphangioleiomyomatosis (LAM) is a slow-progressing metastatic disease that is driven by mutations in the tumor suppressor tuberous sclerosis complex 1/2 (TSC1/2). Rapamycin inhibits LAM cell proliferation and is the only approved treatment, but it cannot cause the regression of existing lesions and can only stabilize the disease. However, in other cancers, immunotherapies such as checkpoint blockade against PD-1 and its ligand PD-L1 have shown promise in causing tumor regression and even curing some patients.

All-optical extravascular laser-ultrasound and photoacoustic imaging of calcified atherosclerotic plaque in excised carotid artery.

Photoacoustic (PA) imaging may be advantageous as a safe, non-invasive imaging modality to image the carotid artery. However, calcification that accompanies atherosclerotic plaque is difficult to detect with PA due to the non-distinct optical absorption spectrum of hydroxyapatite. We propose reflection-mode all-optical laser-ultrasound (LUS) imaging to obtain high-resolution, non-contact, non-ionizing images of the carotid artery wall and calcification.

Deposition of insoluble elastin by pulmonary fibroblasts from patients with COPD is increased by treatment with versican siRNA.

A reduced content of alveolar elastic fibers is a key feature of COPD lung. Despite continued elastogenic potential by alveolar fibroblasts in the lung affected by COPD, repair of elastic fibers does not take place, which is due to increased levels of the chondroitin sulfate proteoglycan versican that inhibits the assembly of tropoelastin into fibers. In this study, primary pulmonary fibroblast cell lines from COPD and non-COPD patients were treated with a small interfering RNA (siRNA) against versican to determine if knockdown of versican could restore the deposition of insoluble elastin.

Versican Deficiency Significantly Reduces Lung Inflammatory Response Induced by Polyinosine-Polycytidylic Acid Stimulation.

Viral infection is an exacerbating factor contributing to chronic airway diseases, such as asthma, via mechanisms that are still unclear. Polyinosine-polycytidylic acid (poly(I:C)), a Toll-like receptor 3 (TLR3) agonist used as a mimetic to study viral infection, has been shown to elicit inflammatory responses in lungs and to exacerbate pulmonary allergic reactions in animal models. Previously, we have shown that poly(I:C) stimulates lung fibroblasts to accumulate an extracellular matrix (ECM), enriched in hyaluronan (HA) and its binding partner versican, which promotes monocyte adhesion.

Single embryo transfer for all?

Historically to maintain live birth rates for women undergoing in vitro fertilisation (IVF), multiple embryos were transferred. Improvements in technology have meant a move to selective single embryo transfer (SET). Do we now have enough confidence in SET to make it mandatory?

Subepithelial Accumulation of Versican in a Cockroach Antigen-Induced Murine Model of Allergic Asthma.

The extracellular matrix (ECM) is an important contributor to the asthmatic phenotype. Recent studies investigating airway inflammation have demonstrated an association between hyaluronan (HA) accumulation and inflammatory cell infiltration of the airways. The ECM proteoglycan versican interacts with HA and is important in the recruitment and activation of leukocytes during inflammation.

G1 Domain of Versican Regulates Hyaluronan Organization and the Phenotype of Cultured Human Dermal Fibroblasts.

Variants of versican have wide-ranging effects on cell and tissue phenotype, impacting proliferation, adhesion, pericellular matrix composition, and elastogenesis. The G1 domain of versican, which contains two Link modules that bind to hyaluronan (HA), may be central to these effects. Recombinant human G1 (rhG1) with an N-terminal 8 amino acid histidine (His) tag, produced in Nicotiana benthamiana, was applied to cultures of dermal fibroblasts, and effects on proliferation and pericellular HA organization determined.

Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts.

COPD lung is characterized by loss of alveolar elastic fibers and an increase in the chondroitin sulfate (CS) matrix proteoglycan versican V1 (V1). V1 is a known inhibitor of elastic fiber deposition and this study investigates the effects of knockdown of V1, and add-back of CS, on CCL-210 lung fibroblasts treated with cigarette smoke extract (CSE) as a model for COPD. CSE inhibited fibroblast proliferation, viability, tropoelastin synthesis, and elastin deposition, and increased V1 synthesis and secretion.

Analysis of peri-islet CD45-positive leucocytic infiltrates in long-standing type 1 diabetic patients.

Aims/hypothesis: The role of peri-islet CD45-positive leucocytes, as one component of insulitis, in beta cell death during human type 1 diabetes remains unclear. We undertook a case study, comparing and quantifying leucocytes in the peri- and intra-islet areas in insulin-positive and -negative islets, to assess whether peri-islet leucocytes are pathogenic to beta cells during type 1 diabetes.

Methods: Pancreatic sections from 12 diabetic patients (0.

Use of versican variant V3 and versican antisense expression to engineer cultured human skin containing increased content of insoluble elastin.

Skin substitutes for repair of dermal wounds are deficient in functional elastic fibres. We report that the content of insoluble elastin in the dermis of cultured human skin can be increased though the use of two approaches that enhance elastogenesis by dermal fibroblasts, forced expression of versican variant V3, which lacks glycosaminoglycan (GAG) chains, and forced expression of versican antisense to decrease levels of versican variant V1 with GAG chains. Human dermal fibroblasts transduced with V3 or anti-versican were cultured under standard conditions over a period of 4 weeks to produce dermal sheets, with growth enhanced though multiple seedings for the first 3 weeks.

Versican and the control of inflammation.

Versican is an extracellular matrix (ECM) proteoglycan that interacts with cells by binding to non-integrin and integrin receptors and to other ECM components that associate with the cell surface. Recent studies have shown also that versican interacts with myeloid and lymphoid cells promoting their adhesion and production of inflammatory cytokines. Versican is produced by stromal cells, as well as leukocytes, and is markedly increased in inflammation.

Versican and the regulation of cell phenotype in disease.

Background: Versican is an extracellular matrix (ECM) proteoglycan that is present in the pericellular environment of most tissues and increases in many different diseases. Versican interacts with cells to influence the ability of cells to proliferate, migrate, adhere and assemble an ECM.

Scope Of Review: The structure of the versican molecule is briefly reviewed and studies highlighting those factors that promote versican synthesis and degradation and their impact on cell phenotype in disease are discussed.

High live birth rate in the subsequent IVF cycle after first-cycle poor response among women with mean age 35 and normal FSH.

Poor ovarian response in IVF cycles is associated with diminished ovarian reserve and poor pregnancy outcome. Little is known about pregnancy outcome after a poor response in women with a normal ovarian reserve. This retrospective study studied women undergoing IVF/intracytoplasmic sperm injection between January 2003 to December 2008 in the FertilityPLUS Clinic in Auckland, New Zealand.

Prevention of alveolar destruction and airspace enlargement in a mouse model of pulmonary lymphangioleiomyomatosis (LAM).

Pulmonary lymphangioleiomyomatosis (LAM) is a rare genetic disease characterized by neoplastic growth of atypical smooth muscle-like LAM cells, destruction of lung parenchyma, obstruction of lymphatics, and formation of lung cysts, leading to spontaneous pneumothoraces (lung rupture and collapse) and progressive loss of pulmonary function. The disease is caused by mutational inactivation of the tumor suppressor gene tuberous sclerosis complex 1 (TSC1) or TSC2. By injecting TSC2-null cells into nude mice, we have developed a mouse model of LAM that is characterized by multiple random TSC2-null lung lesions, vascular endothelial growth factor-D expression, lymphangiogenesis, destruction of lung parenchyma, and decreased survival, similar to human LAM.

Fiber-optic bronchoscope and detection of lung cancer: a five year study.

White light bronchoscopy [WLB] has been used for identification and localization of intra-epithelial pre-neoplastic and neoplastic lesions within the bronchus. Aim of the study was to evaluate the uses of WLB to detect and localize the precancerous and cancerous lesions, and in addition to analyze morphologic presentation, and association to histological type and the variation between genders.A total of 4983 patients were examined by WLB from 2004 to 2009 in a local tertiary teaching hospital.

Pro-inflammatory phenotype of COPD fibroblasts not compatible with repair in COPD lung.

Chronic obstructive pulmonary disease (COPD) is characterized by loss of elastic fibres from small airways and alveolar walls, with the decrease in elastin increasing with disease severity. It is unclear why there is a lack of repair of elastic fibres. We have examined fibroblasts cultured from lung tissue from subjects with or without COPD to determine if the secretory profile explains lack of tissue repair.

Pulmonary fibroblasts from COPD patients show an impaired response of elastin synthesis to TGF-β1.

Insufficiency of tissue repair by pulmonary fibroblasts may contribute to the decrease in elastic fibres in chronic obstructive pulmonary disease (COPD). In this study, the repair function of COPD fibroblasts was assessed by examining the response to transforming growth factor (TGF)-β1. Primary pulmonary fibroblasts were cultured from lung tissue of COPD patients and smoking control subjects.

Neointima formed by arterial smooth muscle cells expressing versican variant V3 is resistant to lipid and macrophage accumulation.

Objective: Extracellular matrix (ECM) of neointima formed following angioplasty contains elevated levels of versican, loosely arranged collagen, and fragmented deposits of elastin, features associated with lipid and macrophage accumulation. ECM with a low versican content, compact structure, and increased elastic fiber content can be achieved by expression of versican variant V3, which lacks chondroitin sulfate glycosaminoglycans. We hypothesized that V3-expressing arterial smooth muscle cells (ASMC) can be used to form a neointima resistant to lipid and macrophage accumulation associated with hypercholesterolemia.