The transcriptomic signature of myostatin inhibitory influence on the differentiation of mouse C2C12 myoblasts

GDF8 (myostatin) is a unique cytokine strongly affecting the skeletal muscle phenotype in human and animals. The aim of the present study was to elucidate the molecular mechanism of myostatin influence on the differentiation of mouse C2C12 myoblasts, using the global-transcriptome analysis with the DNA microarray technique. Treatment with exogenous GDF8 strongly affected the growth and development of C2C12 mouse myoblasts. This was manifested by the inhibition of proliferation and differentiation as well as the impairment of cell fusion. DNA microarray analysis revealed 778 genes regulated by GDF8 in differentiating myoblasts (436 down-regulated and 235 up-regulated). Ontological analysis revealed their involvement in 17 types of biological processes, 10 types of molecular functions and 68 different signalling pathways. The effect of GDF8 was mainly mediated by the disruption of the cell cycle, calcium and insulin signalling pathways and expression of cytoskeletal and muscle specific proteins. The identified key-genes that could play a role as GDF8 targets in differentiating myoblasts are: Mef2, Hgf, Ilb1, Itgb1, Edn1, Ppargc1a

Transcriptional pattern of TGF-beta1 inhibitory effect on mouse C2C12 myoblasts differentiation

The aim of the present study was to define the effect of TGF-β1 on C2C12 myoblasts myogenesis. TGF-β1 together with its receptor is a negative auto-paracrine regulator of myogenesis, which influences the proliferation, differentiation, and functions of muscle cells. TGF-β1 exerts highly significant inhibitory effect on differentiation of C2C12 mouse myoblasts manifested by the impairment of cell fusion and very low expression of myosin heavy chain. The study of differentiating C2C12 mouse myoblasts treated with TGF-β1 revealed 502 genes (436 down-regulated and 66 up-regulated) with statistically different expression. TGF-β1-regulated genes were identified to be involved in 29 biological processes, 29 molecular functions groups and 59 pathways. The strongest inhibiting effect of TGF-β1 was observed in the cadherin and Wnt pathways. The key-genes that could play the role of TGF-β1 targets during myoblasts differentiation was identified such as: Max, Creb1, Ccna2, Bax, MdfI, Tef, Tubg1, Cxcl5, Rho, Calca and Lgals4

MicroRNAs fingerprint of bicuspid aortic valve

none9siAortic valve tissue is largely exposed to high blood flow. Cells belonging to aortic valve tissues are able to detect and respond to flow conditions changes. Bicuspid aortic valve (BAV) presents altered morphology, with only two abnormal cusps instead of three. This results in an alteration of blood flow dynamics on valve cusps and aortic wall, which may, in turn, increase the risk to develop aortic stenosis and/or regurgitation, endocarditis, aortopathy and/or aortic dissection. MicroRNAs (miRNAs) are short RNA strands regulating gene expression mainly through the inhibition of their target mRNAs. They are largely involved in cardiovascular pathophysiology and heart disease. More recently, it has been observed that the expression of specific miRNAs can be modulated in response to changes in hemodynamic conditions. Using a bioinformatic approach, this article analyses available scientific evidence about the differential expression of miRNAs in the bicuspid aortic valve, with a focus on the differential modulation compared to the calcific-degenerative tricuspid aortic valve.noneSabatino J.; Wicik Z.; De Rosa S.; Eyileten C.; Jakubik D.; Spaccarotella C.; Mongiardo A.; Postula M.; Indolfi C.Sabatino, J.; Wicik, Z.; De Rosa, S.; Eyileten, C.; Jakubik, D.; Spaccarotella, C.; Mongiardo, A.; Postula, M.; Indolfi, C

Nutritional Regulation of Mammary miRNome: Implications for Human Studies

Mammary gland is the organ of milk component synthesis that provides the nutrients for growth and development of the mammalian neonate. In addition to macronutrients like proteins, carbohydrates, and lipids known for their roles in providing substrate and energy, a new class of components has been identified notably microRNA that have signaling roles regulating a large set of biological processes. MicroRNAs, short noncoding RNAs, have been reported to act on the mammary tissues, influencing mammary development and milk component biosynthesis, and evidence is now assembling that they also signal to the infant. The expression profile of these miRNAs can be under nutritional regulation. Their presence in milk and their relative persistency through industrial treatment open new way of investigations to use them as biomarkers of animal health, as well as to evaluate their effects on the health of those consuming them. Due to the role of miRNAs on human health and diseases, their transfer from milk or milk products to infants and adults is being actively researched, though their bioavailability is not known. Research is defining their distribution in the different fractions of milk (such as cells, exosomes, fat globule, or skim milk). Indeed, the unique packaging of miRNAs could be crucial for their action through the intestinal tract. The value of milk miRNAs to diverse aspects of human health is now an emerging field of scienc