bims-stacyt 2018-01-28 papers

Peptides. 2018 Jan 17. pii: S0196-9781(18)30017-2. [Epub ahead of print]101 135-144

Induction by innate defence regulator peptide 1018 of pro-angiogenic molecules and endothelial cell migration in a high glucose environment.

Paulina Marin-Luevano, Valentin Trujillo, Adrian Rodriguez-Carlos, Irma González-Curiel, Jose A Enciso-Moreno, Robert E W Hancock, Bruno Rivas-Santiago.

Synthetic innate defence regulator (IDR) peptides such as IDR-1018 modulate immunity to promote key protective functions including chemotaxis, wound healing, and anti-infective activity, while suppressing pro-inflammatory responses to non-pathological levels. Here we demonstrated that IDR-1018 induced, by up to 75-fold, pro-angiogenic VEGF-165 in keratinocytes but suppressed this isoform in endothelial cells. It also induced early angiogenin and prolonged anti-inflammatory TGFβ expression on endothelial cells, while suppressing early pro-inflammatory IL-1β expression levels. IDR-1018 also down-regulated the hypoxia induced transcription factor HIF-1α in both keratinocytes and endothelial cells. Consistent with these data, in an in vitro wound healing scratch assay, IDR-1018 induced migration of endothelial cells under conditions of hypoxia while in epithelial cells migration increased only under conditions of normoxia.

Keywords: Angiogenesis; Angiogenin; Diabetic foot ulcer; IDR-1018; VGF; Wound healing

DOI: https://doi.org/10.1016/j.peptides.2018.01.010

Front Cell Dev Biol. 2017 ;5 119

Metabolism and Transcription in Cancer: Merging Two Classic Tales.

Natalia Martín-Martín, Arkaitz Carracedo, Verónica Torrano.

Cellular plasticity, or the ability of a cancer cell to adapt to changes in the microenvironment, is a major determinant of cell survival and functionality that require the coordination of transcriptional programs with signaling and metabolic pathways. In this scenario, these pathways sense and integrate nutrient signals for the induction of coordinated gene expression programs in cancer. This minireview focuses on recent advances that shed light on the bidirectional relationship between metabolism and gene transcription, and their biological outcomes in cancer. Specifically, we will discuss how metabolic changes occurring in cancer cells impact on gene expression, both at the level of the epigenetic landscape and transcription factor regulation.

Keywords: DNA and histone methylation; cancer metabolism; gene expression regulation; histone acetylation; nutrient sensing networks; transcription factors

DOI: https://doi.org/10.3389/fcell.2017.00119

Neuroscience. 2018 Jan 15. pii: S0306-4522(18)30039-3. [Epub ahead of print]

Microglia and neonatal brain injury.

Carina Mallard, Marie-Eve Tremblay, Zinaida S Vexler.

Microglial cells are now recognized as the "gate-keepers" of healthy brain microenvironment with their disrupted functions adversely affecting neurovascular integrity, neuronal homeostasis, and network connectivity. The perception that these cells are purely toxic under neurodegenerative conditions has been challenged by a continuously-increasing understanding of their complexity, the existence of a broad array of microglial phenotypes, and their ability to rapidly change in a context-dependent manner to attenuate or exacerbate injuries of different nature. Recent studies have demonstrated that microglial cells exert crucial physiological functions during embryonic and postnatal brain development, some of these functions being unique to particular stages of development, and extending far beyond sensing dangerous signals and serving as antigen presenting cells. In this focused review we cover the roles of microglial cells in regulating embryonic vasculogenesis, neurogenesis, and establishing network connectivity during postnatal brain development. We further discuss context-dependent microglial contribution to neonatal brain injuries associated with prenatal and postnatal infection and inflammation, in relation to neurodevelopmental disorders, as well as perinatal hypoxia-ischemia and arterial focal stroke. We also emphasize microglial phenotypic diversity, notably at the ultrastructural level, and their sex-dependent influence on the pathophysiology of neurodevelopmental disorders.

Keywords: Electron microscopy; Hypoxia-ischemia; Inflammation; Perinatal stroke; Synapse; Toll-like receptors

DOI: https://doi.org/10.1016/j.neuroscience.2018.01.023