Journal of cellular biochemistry
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The ERK-MAPK signaling pathway plays a pivotal role during mesenchymal stem cell (MSC) differentiation. Studies have demonstrated that ERK-MAPK promotes adipogenesis and osteogenesis through the phosphorylation of differentiation-associated transcription factors and that it is the only active signaling in all three lineages (adipogenic, chondrogenic, and osteogenic) during MSC differentiation. Recent studies pointed to the significant roles of microRNA-21 (miR-21) during several physiological and pathological processes, especially stem cell fate determination. ⋯ The ERK-MAPK signaling pathway activity had an increasing tendency to respond to miR-21 upregulation and a decreasing tendency to respond to miR-21 down-regulation during the first 4 days of adipogenesis and osteogenesis. Our data indicate that miR-21 modulated ERK-MAPK signaling activity by repressing SPRY2 expression, a known regulator of the receptor tyrosine kinase (RTK) signaling pathway, to affect the duration and magnitude of ERK-MAPK activity. The ERK-MAPK signaling pathway was regulated by Sprouty2 (SPRY2) expression via a miR-21-mediated mechanism during MSC differentiation.
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Establishment of mouse spermatogonial stem cell (SSC) culture systems offers a useful stem cell model for studies of proliferation and self-renewal of mammalian germline stem cells. In addition, spontaneous development of pluripotent stem cells from cultured SSCs emphasizes their possible applications in regenerative medicine as a substitute for embryonic stem cells (ESCs). These pluripotent stem cells termed multipotent germline stem cells (mGSCs) or germline-derived pluripotent stem cells (gPSCs) exhibit almost identical properties in terms of morphology and gene expression patterns to mouse ESCs (mESCs). ⋯ Our results indicated that GFP intensity faithfully reflected cellular states upon reprogramming of SSCs or treatment with a selective extracellular signal-regulated kinase (ERK) inhibitor PD0325901. Moreover, in contrast to mESCs, regulation of Nanog expression did not appear to couple to the Oct4 level in SSCs. Further analysis of Oct4-GFP SSCs demonstrated that a posttranscriptional control of pluripotency marker genes such as Oct4 and Sox2 might play an important role as an inhibitory mechanism preventing the acquisition of pluripotency.
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Increasing evidence demonstrates that target-based agents are active only in molecularly selected populations of patients. Therefore, the identification of predictive biomarkers has become mandatory to improve the clinical development of these novel drugs. Mutations of the epidermal growth factor receptor (EGFR) or rearrangements of the ALK gene in non-small-cell lung cancer, and BRAF mutations in melanoma are clear examples of driver mutations and predictive biomarkers of response to treatment with specific inhibitors. ⋯ In this respect, two different approaches are being developed to introduce a comprehensive molecular characterization in clinical practice: high throughput genotyping platforms, which allow the detection of recognized genetic aberrations in clinical samples, and next generation sequencing that can provide information on all the different types of cancer-causing alterations. The introduction of these techniques in clinical practice will increase the possibility to identify molecular targets in each individual patient, and will also allow to follow the molecular evolution of the disease during the treatment. By using these approaches, the development of personalized medicine for patients with cancer will finally become possible.
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Water homeostasis of the nervous system is important during neural signal transduction. Astrocytes are crucial in water transport in the central nervous system under both physiological and pathological conditions. To date, five aquaporins (AQP) have been found in rat brain astrocytes. ⋯ The p38 inhibitor can inhibit the AQP4 and AQP9 expressions in cultured astrocytes. AQP expression is directly related to the extracellular hyperosmotic stimuli. Moreover, different AQPs can be regulated by a distinct MAPK signal transduction pathway.
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Comparative Study
The Mycobacterium DosR regulon structure and diversity revealed by comparative genomic analysis.
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), which claims approximately two million people annually, remains a global health concern. The non-replicating or dormancy like state of this pathogen which is impervious to anti-tuberculosis drugs is widely recognized as the culprit for this scenario. The dormancy survival regulator (DosR) regulon, composed of 48 co-regulated genes, is held as essential for Mtb persistence. ⋯ The DosR regulon enables the pathogen to persist during lengthy hypoxia. Comparative genomic analysis demonstrated that the DosR regulon is widely distributed among the mycobacterial genomes, ranging from the pathogenic strains to the environmental strains. In-depth studies on the DosR response should provide insights into its role in TB latency in vivo and shape new measures to combat this exceeding recalcitrant pathogen.