Search results for "Cell Differentiation"

FSHD muscular dystrophy region gene 1 binds Suv4-20h1 histone methyltransferase and impairs myogenesis.

2013

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant myopathy with a strong epigenetic component. It is associated with deletion of a macrosatellite repeat leading to over-expression of the nearby genes. Among them, we focused on FSHD region gene 1 (FRG1) since its over-expression in mice, Xenopus laevis and Caenorhabditis elegans, leads to muscular dystrophy-like defects, suggesting that FRG1 plays a relevant role in muscle biology. Here we show that, when over-expressed, FRG1 binds and interferes with the activity of the histone methyltransferase Suv4-20h1 both in mammals and Drosophila. Accordingly, FRG1 over-expression or Suv4-20h1 knockdown inhibits myogenesis. Moreov…

Differentiation of Murine C2C12 Myoblasts Strongly Reduces the Effects of Myostatin on Intracellular Signaling

2020

Alongside in vivo models, a simpler and more mechanistic approach is required to study the effects of myostatin on skeletal muscle because myostatin is an important negative regulator of muscle size. In this study, myostatin was administered to murine (C2C12) and human (CHQ) myoblasts and myotubes. Canonical and noncanonical signaling downstream to myostatin, related ligands, and their receptor were analyzed. The effects of tumorkines were analyzed after coculture of C2C12 and colon cancer-C26 cells. The effects of myostatin on canonical and noncanonical signaling were strongly reduced in C2C12 cells after differentiation. This may be explained by increased follistatin, an endogenous blocke…

Drug connectivity mapping and functional analysis reveal therapeutic small molecules that differentially modulate myelination

2022

Disruption or loss of oligodendrocytes (OLs) and myelin has devastating effects on CNS function and integrity, which occur in diverse neurological disorders, including Multiple Sclerosis (MS), Alzheimer’s disease and neuropsychiatric disorders. Hence, there is a need to develop new therapies that promote oligodendrocyte regeneration and myelin repair. A promising approach is drug repurposing, but most agents have potentially contrasting biological actions depending on the cellular context and their dose-dependent effects on intracellular pathways. Here, we have used a combined systems biology and neurobiological approach to identify compounds that exert positive and negative effects on olig…

Signalling through TLR2/MyD88 induces differentiation of murine bone marrow stem and progenitor cells to functional phagocytes in response to Candida…

2009

Summary We have previously demonstrated that inactivated yeasts and hyphae of Candida albicans induce in vitro the proliferation of murine haematopoietic stem and progenitor cells (HSPCs, sorted as LKS cells: Lin - c-Kit + Sca-1 + ) as well as their differentia- tion to lineage-positive cells, through a MyD88- dependent pathway. In this work, we have found that this process is mainly mediated by TLR2, and that expanding cells express myeloid and not lym- phoid markers. Incubation of long-term repopulat- ing HSCs (Lin - CD105 + and Sca-1 + ) with C. albicans yeasts resulted in their proliferation and up regu- lation of the common myeloid progenitors (CMPs) markers, CD34 and FcgRII/III, by a …

Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated au…

2012

AbstractAntineutrophil cytoplasmic antibodies (ANCAs) target proteins normally retained within neutrophils, indicating that cell death is involved in the autoimmunity process. Still, ANCA pathogenesis remains obscure. ANCAs activate neutrophils inducing their respiratory burst and a peculiar form of cell death, named NETosis, characterized by formation of neutrophil extracellular traps (NETs), decondensed chromatin threads decorated with cytoplasmic proteins endorsed with antimicrobial activity. NETs have been consistently detected in ANCA-associated small-vessel vasculitis, and this association prompted us to test whether the peculiar structure of NET favors neutrophil proteins uploading i…

Constant detection of cyclooxygenase 2 in terminal stages of myeloid maturation.

2006

Dexamethasone dipropionate loaded nanoparticles of α-elastin-g-PLGA for potential treatment of restenosis.

2013

A graft copolymer of α-elastin with poly(lactic-co-glycolic) acid (PLGA) has been synthesized and successfully employed to produce nanoparticles. Exploiting the known biological activity of α-elastin to promote the maintenance of smooth muscle cells (SMCs) contractile phenotype and the antiproliferative effect of glucocorticoids, the aim of this research was to produce drug-loaded nanoparticles suitable for potential treatment of restenosis. In particular, nanoparticles of α-elastin-g-PLGA with a mean size of 200 nm have been produced and loaded with dexamethasone dipropionate (10% w/w), chosen as a model drug that inhibits proliferation of vascular SMCs. These nanoparticles are able to pro…

Structure and closure mechanism of the human umbilical artery

1978

The structure of the fully-patent umbilical artery and rearrangement of its structural elements with postnatal closure were examined in 10 centimeter long umbilical cord segments which were double-clamped at different time intervals after delivery. The fully-patent umbilical artery consists of two main layers: an outer layer of circularly arranged smooth muscle cells and an inner layer which shows rather irregularly and loosely arranged cells embedded in abundant metachromatic ground substance. No predominantly longitudinal arrangements of cells and fibers reported by earlier investigators could be identified in the inner layer. Closure of the umbilical arteries is initiated by numerous loc…

High-density ZnO Nanowires as a Reversible Myogenic-Differentiation-Switch

2018

Mesoangioblasts are outstanding candidates for stem-cell therapy and are already being explored in clinical trials. However, a crucial challenge in regenerative medicine is the limited availability of undifferentiated myogenic progenitor cells because growth is typically accompanied by differentiation. Here reversible myogenic-differentiation switching during proliferation is achieved by functionalizing the glass substrate with high-density ZnO nanowires (NWs). Specifically, mesoangioblasts grown on ZnO NWs present a spherical viable undifferentiated cell state without lamellopodia formation during the entire observation time (8 days). Consistently, the myosin heavy chain, typically express…

Autoantibodies in complex regional pain syndrome bind to a differentiation-dependent neuronal surface autoantigen.

2009

Complex regional pain syndrome, which is characterised by pain and trophic disturbances, develops frequently after peripheral limb trauma. There is an increasing evidence of an involvement of the immune system in CRPS, and recently we showed that CRPS patients have autoantibodies against nervous system structures. Therefore we tested the sera of CRPS patients, neuropathy patients and healthy volunteers for surface-binding autoantibodies to primary cultures of autonomic neurons and differentiated neuroblastoma cell lines using flow cytometry. Thirteen of 30 CRPS patients, but none of 30 healthy controls and only one of the 20 neuropathy sera had specific surface binding to autonomic neurons …