The transcription factor Sox2 [SRY (sex-determining region Y)-box 2] is essential for the regulation of self-renewal and homoeostasis of NSCs (neural stem cells) during brain development. However, the downstream targets of Sox2 and its underlying molecular mechanism are largely unknown. In the present study, we found that Sox2 directly up-regulates the expression of survivin, which inhibits the mitochondria-dependent apoptotic pathway in NSCs. Although overexpression of Sox2 elevates survivin expression, knockdown of Sox2 results in a decrease in survivin expression, thereby initiating the mitochondria-dependent apoptosis related to caspase 9 activation. Furthermore, cell apoptosis owing to knockdown of Sox2 can be rescued by ectopically expressing survivin in NSCs as well as in the mouse brain, as demonstrated by an in utero-injection approach. In short, we have found a novel Sox2/survivin pathway that regulates NSC survival and homoeostasis, thus revealing a new mechanism of brain development, neurological degeneration and such aging-related disorders.
Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a massive apoptosis of MCDs in both global FXR gene-deficient mice and collecting duct-specific FXR knockout mice. In vitro studies showed that hypertonicity significantly increased FXR and tonicity response enhancer binding protein (TonEBP) expression in mIMCD3 cell line and primary cultured MCDs. Activation and overexpression of FXR markedly increased cell viability and decreased cell apoptosis under hyperosmotic conditions. In addition, FXR can increase gene expression and nuclear translocation of TonEBP. We conclude that FXR protects MCDs from hypertonicity-induced cell injury very likely via increasing TonEBP expression and nuclear translocation. This study provides insights into the molecular mechanism by which FXR enhances urine concentration via maintaining cell viability of MCDs under hyperosmotic condition.
NAG-targeting fluorescent probe for sensing proximal tubule cells in patient's crude urine and precision diagnosis for kidney injury unit.
In recent years, metabolic disorder, especially fatty liver disease, has been considered a major challenge to global health. The attention of researchers focused on expanding knowledge of the regulation mechanism behind these diseases and towards the new diagnostics tools and treatments. The pathophysiology of the fatty liver disease is undoubtedly complex. Abnormal hepatic lipid accumulation is a major symptom of most metabolic diseases. Therefore, the identification of novel regulation factors of lipid metabolism is important and meaningful. As a new diagnostic tool, the function of microRNAs during fatty liver disease has recently come into notice in biological research. Accumulating evidence supports the influence of miRNAs in lipid metabolism. In this review, we discuss the potential role of miRNAs in liver lipid metabolism and the pathogenesis of fatty liver disease.
Synaptic hypothesis of schizophrenia suggests that alterations of synaptic transmission and neuronal connectivity might be core feature of schizophrenia. STON2 participates in synaptic vesicle protein recognition and neural endocytosis. To explore the association of STON2 with schizophrenia, 11 single nucleotide polymorphisms (SNPs) were examined in 768 Chinese Han schizophrenia cases and 1347 Chinese Han controls. The results showed that three SNPs had strong association with schizophrenia, two exonic SNPs (rs2241621: allelic P=0.0005; rs3813535: allelic P=0.0078) and one intronic SNP (rs9323698: allelic P=0.0019). When haplotype analysis performed, two linkage disequilibrium blocks showed significant differences in frequency between cases and controls. Notably, our data displays an over-transmitted functional haplotype C-C (Pro307-Ala851) in schizophrenia cases. Our results suggest STON2 may be a susceptibility gene for schizophrenia.
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