Periostin in Inflammatory Bowel Disease (IBD) development and synergistic effects mediated via CCL5

The incidence of IBD is rising all over the world and is affecting 1 in 4000 people in Europe and 1 in 16.000 in Asia. [1] Welldocumented, reliable numbers for Kazakhstan are currently not available but observations from local physicians (personal communication) suggest that numbers might be significantly higher than suggested by the literature. The matricellular protein Periostin has recently been shown to be involved in IBD [2] (and our own unpublished data). In a chemically induced murine model (dextrane sulfate sodium DSS) it mediates intestinal inflammation through the activation of NF-κB signaling, which suggests that periostin is a potential therapeutic target for inflammatory bowel disease [2]. CCL5, also know as RANTES, is a chemokine shown to be interacting with the G protein-coupled receptors CCR1, CCR3 and CCR5 [3]. In a recent study it could be shown that CCR5 expression correlates with the infiltration of inflammatory cells into the lamina propria of IBD patients [4]. Periostin is a matricellular protein originally isolated from osteoblasts and found to be preferentially expressed in the periosteum [5, 6]. Periostin contains an N-terminal secretory signal peptide, followed by a cysteine-rich domain, four internal homologous repeats, and a C-terminal hydrophilic domain. The four internal repeats exhibit homology to the axon guidance protein fasciclin I that is involved in the development of nervous system in invertebrates and were thus named fasciclin domains

The c-ros tvrosine kinase receptor I controls regionalization and differehiation of epithelial cells in the epididymis

The c-ros gene was originally identified in mutant form as an oncogene. The proto-oncogene encodes a tyrosine kinase receptor that is expressed in a small number of epithelial cell types, including those of the epididymis. Targeted mutations of c-ros in the mouse reveal an essential role of the gene in male fertility. Male c-ros -1- animals do not reproduce, whereas the fertility of female animals is not affected. We demonstrate that c-ros is not required in a cell autonomous manner for male germ cell development or function. The gene, therefore, does not affect sperm generation or function in a direct manner. The primary defect in the mutant animals was located in the epididymis, showing that c-ros controls appropriate development of the epithelia, particularly regionalization and terminal differentiation. The epididymal defect does not interfere with production or storage of sperm but, rather, with sperm maturation and the ability of sperm to fertilize in vivo. Interestingly, sperm isolated from c-ros - / - animals can fertilize in vitro. Our results highlight the essential role of the epididymis in male fertility and demonstrate a highly specific function of the c-ros receptor tyrosine kinase during development of distinct epithelial cell

The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration

Matrilins are adaptor proteins of the extracellular matrix involved in the formation of both collagen-dependent and collagen-independent filamentous networks. Although their molecular structure and binding partners have been characterized, the functional roles of the four matrilin family members in vivo are still largely unknown. Here, we show that matrilin 2, expressed in pre-myelinating Schwann cells during normal development, profoundly influences the behaviour of glial cells and neurons in vitro. When offered as a uniform substrate, matrilin 2 increased neurite outgrowth of dorsal root ganglia (DRG) neurons and enhanced the migration of both cell line- and embryonic DRG-derived Schwann cells. Vice versa, axonal outgrowth and cell migration were decreased in DRG cultures prepared from matrilin-2-deficient mice compared with wild-type (wt) cultures. In stripe assays, matrilin 2 alone was sufficient to guide axonal growth and, interestingly, axons favoured the combination of matrilin 2 and laminin over laminin alone. In vivo, matrilin 2 was strongly upregulated in injured peripheral nerves of adult wild-type mice and failure of protein upregulation in knockout mice resulted in delayed regrowth of regenerating axons and delayed time-course of functional recovery. Strikingly, the functional recovery 2 months after nerve injury was inferior in matrilin-2-deficient mice compared with wild-type littermates, although motoneuron survival, quality of axonal regeneration, estimated by analyses of axonal diameters and degrees of myelination, and Schwann cell proliferation were not influenced by the mutation. These results show that matrilin 2 is a permissive substrate for axonal growth and cell migration, and that it is required for successful nerve regeneratio

Progenitor cells of the testosterone-producing Leydig cells revealed

The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair

Peripheral nervous system defects in erbB2 mutants following genetic rescue of heart development

The ErbB2 tyrosine kinase functions as coreceptor for the neuregulin receptors ErbB3 and ErbB4 and can participate in signaling of EGF receptor (ErbB1), interleukin receptor gp130, and G-protein coupled receptors. ErbB2−/− mice die at midgestation because of heart malformation. Here, we report a genetic rescue of their heart development by myocardial expression of erbB2 cDNA that allows survival of the mutants to birth. In rescued erbB2 mutants, Schwann cells are lacking. Motoneurons form and can project to muscle, but nerves are poorly fasciculated and disorganized. Neuromuscular junctions form, as reflected in clustering of AChR and postsynaptic expression of the genes encoding the a-AChR, AChE, e-AChR, and the RI subunit of the cAMP protein kinase. However, a severe loss of motoneurons on cervical and lumbar, but not on thoracic levels occurs. Our results define the roles of Schwann cells during motoneuron and synapse development, and reveal different survival requirements for distinct motoneuron population

Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis and ocular integrity in mice

Sebocytes, which are characterized by lipid accumulation that leads to cell disruption, can be found in hair follicle-associated sebaceous glands (SGs) or in free SGs such as the Meibomian glands in the eyelids. Because genetic tools that allow targeting of sebocytes while maintaining intact epidermal lipids are lacking, the relevance of sebaceous lipids in health and disease remains poorly understood. Using Scd3, which is expressed exclusively in mature sebocytes, we established a mouse line with sebocyte-specific expression of Cre recombinase. Both RT-PCR analysis and crossing into Rosa26-lacZ reporter mice and KrasG12D mice confirmed Cre activity specifically in SGs, with no activity in other skin compartments. Importantly, loss of SCD3 function did not cause detectable phenotypical alterations, endorsing the usefulness of Scd3-Cre mice for further functional studies. Scd3-Cre-induced, diphtheria chain A toxin-mediated depletion of sebaceous lipids resulted in impaired water repulsion and thermoregulation, increased rates of UVB-induced epidermal apoptosis and caused a severe pathology of the ocular surface resembling Meibomian gland dysfunction. This novel mouse line will be useful for further investigating the roles of sebaceous lipids in skin and eye integrity

Some physical and mechanical characterization of Tunisian planted Eucalytus loxophleba and Eucalyptus salmonophloia woods

After the independence in 1957 and with the support of the FAO117, Eucalyptus species were planted in Tunisia in different arboreta throughout the country for close observation and adaptation to climate and soil. The objective of this study is to evaluate the physical and mechanical properties of two species planted in marginal area in Sousse (arboretum El Hanya) in the east of Tunisia (Eucalytus loxophleba and Eucalyptus salmonophloia). The moisture content, specific gravity and volumetric shrinkage were measured. The Mechanical tests were performed to evaluate the hardness, the static bending and the resistance to compression parallel to fiber direction. Preliminary results showed that Eucalytusloxophleba and Eucalyptus salmonophloia have a low dimensional stability. During the drying period, woods showed signs of collapses. On the other hand, both species were highly resistant to compression strength while they were lower on the static bending. Eucalytus loxophleba and Eucalyptus salmonophloia characteristics established within this study were similar to other Eucalyptus species from Tunisia, Morocco, Australia and Brazil. This wood may be used in furniture, structural material and/or biomass energy. (Résumé d'auteur

PERIOSTIN IN ALLERGY AND INFLAMMATION

Matricellular proteins are involved in the crosstalk between cells and their environment and thus play an important role in allergic and inflammatory reactions. Periostin, a matricellular protein, has several documented and multi-faceted roles in health and disease. It is differentially expressed, usually upregulated, in allergic conditions, a variety of inflammatory diseases as well as in cancer and contributes to the development and progression of these diseases. Periostin has also been shown to influence tissue remodelling, fibrosis, regeneration and repair. In allergic reactions periostin is involved in type 2 immunity and can be induced by IL-4 and IL-13 in bronchial cells. A variety of different allergic diseases, among them bronchial asthma and atopic dermatitis (AD), have been shown to be connected to periostin expression. Periostin is commonly expressed in fibroblasts and acts on epithelial cells as well as fibroblasts involving integrin and NF-κB signalling. Also direct signalling between periostin and immune cells has been reported. The deposition of periostin in inflamed, often fibrotic, tissues is further fuelling the inflammatory process. There is increasing evidence that periostin is also expressed by epithelial cells in several of the above-mentioned conditions as well as in cancer. Augmented periostin expression has also been associated with chronic inflammation such as in inflammatory bowel disease (IBD). Periostin can be expressed in a variety of different isoforms, whose functions have not been elucidated yet. This review will discuss potential functions of periostin and its different isoforms in allergy and inflammation

Anticancer activity of metformin: a systematic review of the literature

https://www.ncbi.nlm.nih.gov/pubmed/31534778BACKGROUND: The anticancer activity of metformin has been confirmed against several cancer types in vitro and in vivo. However, the underlying mechanisms of metformin in the treatment of cancer are not fully understood. This systematic review aims to discuss the possible anticancer mechanism of action of metformin. METHOD: A search through different databases was conducted, including Medline and EMBASE. RESULTS: A total of 96 articles were identified of which 56 were removed for duplication and 24 were excluded after reviewing the title and abstract. A total of 12 research articles were included that describe different antiproliferative mechanisms that may contribute to the antineoplastic effects of metformin. CONCLUSION: This analysis discussed the potential anticancer activity of metformin and highlighted the importance of AMPK as a potential target for anticancer therapy

Efficient transfer of HSV-1 amplicon vectors into embryonic stem cells and their derivatives

The derivation of specialized differentiated cells from embryonic stem (ES) cells is now a major focus for future therapies involving cell and organ replacement in humans. To obtain populations of differentiated cells for transplantation into the human body, highly optimized protocols are needed that allow direction of the development of ES cells and their derivatives. These protocols mostly include the use of a combination of growth factors that control the differentiation of ES cells into highly specialized cells found in adult organs. The introduction of different growth factors into ES cells and their derivatives via viral gene transfer may greatly facilitate the optimization of these protocols. In this chapter, we describe a method based on herpes simplex virus type 1, which allows efficient gene transfer during several steps of a protocol, directed to obtain neural progenitors from ES cells. This protocol therefore may allow the study of potential factors influencing the cell fate or differentiation of ES cells and their derivatives