FBLN2 (fibulin 2)

Fibulin-2 is an extracellular matrix glycoprotein with an important function in maintaining elastic properties in different tissues. Fibulin-2 belongs to a protein family with seven members characterized by sharing a globular domain at the carboxy-terminus, which is called ""fibulin-like"", ""FC domain"" or domain III. Together with fibulin-1, fibulin-2 forms the so called subgroup 1 in the fibulin family which contains three anaphylatoxin modules in their sequence. Fibulin-2 does not only form part of elastic fibers but is also present in basement membranes and other connective tissue structures. Besides its structural function, alterations in fibulin-2 expression have also been related to several pathological processes. Thus, fibulin-2 has been shown to be implicated in blood pressure regulation, vascular injury protection or with a protective role in some heart malfunctioning. Also, fibulin-2 participation has been described in cancer showing both oncogenic or tumor-suppressor properties

Cooperation by fibroblasts and bone marrow-mesenchymal stem cells to improve pancreatic rat-to-mouse islet xenotransplantation.

Experimental and clinical experiences highlight the need to review some aspects of islet transplantation, especially with regard to site of grafting and control of the immune response. The subcutaneous space could be a good alternative to liver but its sparse vasculature is its main limitation. Induction of graft tolerance by using cells with immunoregulatory properties is a promising approach to avoid graft rejection. Both Fibroblasts and Mesenchymal Stem Cells (MSCs) have shown pro-angiogenic and immunomodulatory properties. Transplantation of islets into the subcutaneous space using plasma as scaffold and supplemented with fibroblasts and/or Bone Marrow-MSCs could be a promising strategy to achieve a functional extra-hepatic islet graft, without using immunosuppressive drugs. Xenogenic rat islets, autologous fibroblasts and/or allogenic BM-MSCs, were mixed with plasma, and coagulation was induced to constitute a Plasma-based Scaffold containing Islets (PSI), which was transplanted subcutaneously both in immunodeficient and immunocompetent diabetic mice. In immunodeficient diabetic mice, PSI itself allowed hyperglycemia reversion temporarily, but the presence of pro-angiogenic cells (fibroblasts or BM-MSCs) within PSI was necessary to improve graft re-vascularization and, thus, consistently maintain normoglycemia. In immunocompetent diabetic mice, only PSI containing BM-MSCs, but not those containing fibroblasts, normalized glycemia lasting up to one week after transplantation. Interestingly, when PSI contained both fibroblasts and BM-MSCs, the normoglycemia period showed an increase of 4-times with a physiological-like response in functional tests. Histology of immunocompetent mice showed an attenuation of the immune response in those grafts with BM-MSCs, which was improved by co-transplantation with fibroblasts, since they increased BM-MSC survival. In summary, fibroblasts and BM-MSCs showed similar pro-angiogenic properties in this model of islet xenotransplantation, whereas only BM-MSCs exerted an immunomodulatory effect, which was improved by the presence of fibroblasts. These results suggest that cooperation of different cell types with islets will be required to achieve a long-term functional graft

New Insights into ADAMTS Metalloproteases in the Central Nervous System

Components of the extracellular matrix (ECM) are key players in regulating cellular functions throughout the whole organism. In fact, ECM components not only participate in tissue organization but also contribute to processes such as cellular maintenance, proliferation, and migration, as well as to support for various signaling pathways. In the central nervous system (CNS), proteoglycans of the lectican family, such as versican, aggrecan, brevican, and neurocan, are important constituents of the ECM. In recent years, members of this family have been found to be involved in the maintenance of CNS homeostasis and to participate directly in processes such as the organization of perineural nets, the regulation of brain plasticity, CNS development, brain injury repair, axonal guidance, and even the altering of synaptic responses. ADAMTSs are a family of “A disintegrin and metalloproteinase with thrombospondin motifs” proteins that have been found to be involved in a multitude of processes through the degradation of lecticans and other proteoglycans. Recently, alterations in ADAMTS expression and activity have been found to be involved in neuronal disorders such as stroke, neurodegeneration, schizophrenia, and even Alzheimer’s disease, which in turn may suggest their potential use as therapeutic targets. Herein, we summarize the different roles of ADAMTSs in regulating CNS events through interactions and the degradation of ECM components (more specifically, the lectican family of proteoglycans)

Evolution of bioluminescent cells embedded in PSI and subcutaneously transplanted in both immunocompetent and immunodeficient mice.

<p>A) <i>Immunocompetent mice</i>. Relative luminescence signal of 10⁶ allogenic Luc[+]-BM-MSCs transplanted alone into PSI (PSI-5M_luc) or co-transplanted with 10⁶ autologous Luc[-]-fibroblasts (PSI-5FM_luc), as well as representative IVIS® lumina images of previously described mice, 12 days after transplantation. B) <i>Immunodeficient mice</i>. Relative luminescence signal of 10⁶ allogenic Luc[+]-BM-MSCs transplanted alone into PSI (PSI-M_luc) or co-transplanted with 10⁶ autologous Luc[-]-fibroblasts (PSI-FM_luc), as well as luminescence signal of 10⁶ allogenic Luc[+]-fibroblasts transplanted alone into PSI (PSI-F_luc). Representative IVIS® lumina images of previously described mice, 12 days after transplantation. Values related to day 0 (100%) are represented as mean ± SEM. For all groups n=5. (*) p<0.05; (**) p<0.01; (***) p<0.001.</p

Histology of subcutaneous islet xenografts in immunocompetent diabetic mice.

<p>A) Representative images of subcutaneously transplanted islets alone (ISC), PSI without cells and PSI containing: 10⁶ autologous fibroblasts (PSI-5F), 10⁶ allogenic BM-MSCs (PSI-5M), or 10⁶ of both autologous fibroblasts and allogenic BM-MSCs (PSI-5FM). Islet grafts were retrieved seven days after transplantation in diabetic mice. Samples were stained with H and E, or labelled with anti-insulin or anti-MPO antibodies. Black arrows point to islets. B) Quantification of the number of MPO-positive cells per field present on the leukocyte infiltration of the islet graft. C) Quantification of the insulin-positive area per section present on the islet graft. (**) p<0.01; (***) p<0.001.</p

Role of Periostin in Adhesion and Migration of Bone Remodeling Cells.

Periostin is an extracellular matrix protein highly expressed in collagen-rich tissues subjected to continuous mechanical stress. Functionally, periostin is involved in tissue remodeling and its altered function is associated to numerous pathological processes. In orthodontics, periostin plays key roles in the maintenance of dental tissues and it is mainly expressed in those areas where tension or pressing forces are taking place. In this regard, high expression of periostin is essential to promote migration and proliferation of periodontal ligament fibroblasts. However little is known about the participation of periostin in migration and adhesion processes of bone remodeling cells. In this work we employ the mouse pre-osteoblastic MC3T3-E1 and the macrophage-like RAW 264.7 cell lines to overexpress periostin and perform different cell-based assays to study changes in cell behavior. Our data indicate that periostin overexpression not only increases adhesion capacity of MC3T3-E1 cells to different matrix proteins but also hampers their migratory capacity. Changes on RNA expression profile of MC3T3-E1 cells upon periostin overexpression have been also analyzed, highlighting the alteration of genes implicated in processes such as cell migration, adhesion or bone metabolism but not in bone differentiation. Overall, our work provides new evidence on the impact of periostin in osteoblasts physiology