RESUMO
Thyroid hormone (TH) signaling controls muscle progenitor cells differentiation. However, inflammation can alter muscle TH signaling by modulating the expression of TH transporters (Slc16a2), receptors (Thra1), and deiodinase enzymes (Dio2 and Dio3). Thus, a proinflammatory environment could affect myogenesis. The role of a low-grade inflammatory milieu in TH signaling during myogenesis needs further investigation. Herein, we aimed to study the impact of the bacterial lipopolysaccharide (LPS)-induced inflammatory stimulus on the TH signaling during myogenesis. C2C12 myoblasts differentiation was induced without (CTR) or with 10 ng/mL LPS presence. The myoblasts under LPS stimulus release the proinflammatory cytokines (IL-6 and IL-1ß) and chemokines (CCL2 and CXCL-1). LPS decreases Myod1 expression by 28% during the initial myogenesis, thus reducing the myogenic stimulus. At the same time, LPS reduced the expression of Dio2 by 41% but doubled the D2 enzymatic activity. The late differentiation was not affected by inflammatory milieu, which only increased the Slc16a2 gene expression by 38%. LPS altered the intracellular metabolism of TH and reduced the initial myogenic stimulus. However, it did not affect late differentiation. Increased intracellular TH activation may be the compensatory pathway involved in the recovery of myogenic differentiation under a low-grade inflammatory milieu.
RESUMO
Intrathymic lipid-laden multilocular cells (LLMC) are known to express pro-inflammatory factors that might regulate functional activity of the thymus. However, the phenotype of age-associated intrathymic LLMC is still controversial. In this study, we evaluated LLMC density in the aging thymus and better characterized their distribution, ultrastructure and phenotype. Our results show an increased density of LLMC in the thymus from 03 to 24 months of age. Morphologically, intrathymic LLMC exhibit fibroblastoid fusiform, globular or stellate shapes and can be found in the subcapsular region as well as deeper in the parenchyma, including the perivascular area. Some parenchymal LLMC were like telocytes accumulating lipids. We identified lipid droplets with different electrondensities, lipofuscin granules and autolipophagosome-like structures, indicating heterogeneous lipid content in these cells. Autophagosome formation in intrathymic LLMC was confirmed by positive staining for beclin-1 and perilipin (PLIN), marker for lipid droplet-associated proteins. We also found LLMC in close apposition to thymic stromal cells, endothelial cells, mast cells and lymphocytes. Phenotypically, we identified intrathymic LLMC as preadipocytes (PLIN+PPARγ2+), brown adipocytes (PLIN+UCP1+), macrophages (PLIN+Iba-1+) or pericytes (PLIN+NG2+) but not epithelial cells (PLIN- panCK+). These data indicate that intrathymic LLMC are already present in the young thymus and their density significantly increases with age. We also suggest that LLMC, which are morphologically distinct, establish direct contact with lymphocytes and interact with stromal cells. Finally, we evidence that intrathymic LLMC correspond to not only one but to distinct cell types accumulating lipids.
Assuntos
Metabolismo dos Lipídeos , Fenótipo , Timo/citologia , Timo/metabolismo , Fatores Etários , Animais , Autofagia , Comunicação Celular , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Linfócitos/citologia , Linfócitos/metabolismo , Mastócitos/citologia , Mastócitos/metabolismo , Camundongos , Fagossomos/metabolismo , Células Estromais/citologia , Células Estromais/metabolismo , Timócitos/citologia , Timócitos/metabolismoRESUMO
Huntington's disease is a neurodegenerative autosomal disorder characterized by selective loss of striatal and cortical neurons. The mammalian brain subventricular zone contains a population of neural precursors involved in postnatal neurogenesis. These newly generated cells migrate from the subventricular zone along the rostral migratory stream and differentiate into mature olfactory bulb neurons throughout adulthood. The establishment of this pathway depends upon a variety of molecules, including polysialylated neural cell adhesion molecule (PSA-NCAM). We used a murine model of Huntington's disease, the R6/2 transgenic mouse, and in vivo bromodeoxyuridine administration to label cells undergoing proliferation and to follow their migration along the rostral migratory stream. Bromodeoxyuridine labeling did not show any significant increase in proliferation of progenitor cells in symptomatic R6/2 mice, but migration of neuroblasts along the rostral migratory stream was significantly diminished. The decrease in neuroblast migration was not due to an alteration in the expression of PSA-NCAM along the rostral migratory stream since immunohistochemical analysis showed no significant differences between R6/2 and wild type mice. In addition, we used Fluoro-Jade C to evaluate apoptosis and demonstrated that the number of apoptotic cells in the rostral migratory stream is similar in affected and wild type animals, suggesting that cell death is not responsible for the differences observed in neuroblast migration. We conclude that in R6/2 mice, progenitor cells have an impaired migration in their route to the olfactory bulb, with accumulation of cells in the caudal rostral migratory stream that does not result from changes in PSA-NCAM expression and/or cell death.