5/6 nephrectomy (5/6Nx) effect on the brain and liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: naoya matsunaga
PROVIDER: E-GEOD-35136 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Chronic kidney disease (CKD) is a very important problem in global health treatment. CKD increases the disease risk of apoplexy, cardiac failure and cardiac infarction. In addition, neurological complications, including depression and restless legs syndrome, occur in almost all CKD patients; however, the mechanisms of these neurological complications remain unclear. Here, we showed the disruptive effect of chronic renal failure in 5/6 nephrectomy mice on an immobility time of forced swim and tail suspension test and the 24-hr rhythm of Drd2 and clock gene expressions in the striatum. These disruptive effects were induced by abnormal signal transduction in high TGF-M-NM-21 expression from the kidney. Abnormal TGF-M-NM-2 signal in the striatum led to TCF7L2 expression and ID2 induced by TCF7L2 led to disruption of the 24-hr rhythm of clock gene expression. These findings suggest that neurological complications in CKD might be overcome by amelioration of the TGF-M-NM-2 signal. Differential gene expression between 5/6 nephrectomized and sham-operated mouse was measured on the brain.
2013-08-01 | E-GEOD-35134 | biostudies-arrayexpress
Project description:Chronic renal failure (CRF) is associated with a decrease in drug metabolism. The present study investigated the repercussions of CRF on liver cytochrome P450 (CYPs), but the mechanisms have been little explored. On the other hand, the expression of several CYP genes exhibits circadian rhythm. Here we report that downregulation of hepatic CYP3A11 (the murine homolog to human CYP3A4; the most decrease in 5/6Nx using microarray analysis) by suppressing the expression of clock gene; D-site binding protein (DBP). In vivo experiments, the mRNA levels of hepatic CYP3A11 exhibit circadian rhythm regulated by DBP and E4BP4, and significantly decreased in 5/6Nx. Microarray analysis revealed that the general transcription factors of CYP3A11 did not changed. However, DBP were downregulated and several CYP genes controlled by DBP also significantly decreased in 5/6Nx. These downregulations were not observed in angiotensin II type 1alpha receptor (AT II R1a) deficient 5/6Nx because serum TGF-betaM-BM- was not upregulate. In vitro experiments, the RNA levels of CYP3A11 and DBP were downregulated in wild-type mouse hepatocytes incubated with serum from 5/6Nx, but did not changed in Id2 (-/-) hepatocytes. In fact, hepatic Id2 was upregulated and caused the downregulation of DBP in 5/6Nx. Hepatocyte treated with SD208 (TGF-beta receptor 1 selectivity inhibitor) recovered CYP3A11, DBP and Id2 to control levels. Furthermore, 5/6Nx treated with tranilast (inhibitor of TGF-beta production or isolation) or candesartan (ARBs) also recovered CYP3A11 levels. Our findings define that DBP has effects on downregulation of CYP3A11. In CRF conditions, TGF-beta is upregulated by angiotensin II receptor in renal and downregulates DBP and CYP3A11 levels mediated by Id2 in liver. Furthermore, downregulation of CYP3A11 can prevent by tranilast or candesartan. Differential gene expression between 5/6 nephrectomized and sham-operated mouse was measured on the liver.
2013-08-01 | E-GEOD-35135 | biostudies-arrayexpress
Project description:Thymidine phosphorylase (TP) catalyzes the reversible phosphorolysis of thymidine, deoxyuridine, and their analogs to the respective bases and 2-deoxy-D-ribose-1-phosphate. TP is identical to platelet-derived endothelial cell growth factor (PD-ECGF). TP was reported to induce many angiogenic factors. However, the molecular mechanism of the TP function is still obscure. To elucidate the molecular basis for the TP function in human epidermoid carcinoma KB cells, we performed a whole genome-wide microarray analysis. Genes upregulated in KB cells overexpressing TP are supposed to represent potential molecular targets of TP in KB cells. KB cells (4 M-CM-^W 10^5) in 5 ml of culture media were cultured for 24 hours, then the growth medium was replaced with serum-free medium. These cells were maintained at 37 M-KM-^ZC in a humidified atmosphere of 5% CO2 for 12 hours, then these cells were collected for RNA extraction and quantification of the transcripts by microarray analysis.
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2013-08-01 | E-GEOD-39288 | biostudies-arrayexpress
Project description:Adult renal stem/progenitor cells (ARPCs), first identified in the BowmanM-bM-^@M-^Ys capsule, were recently identified also in the tubular compartment and it was demonstrated that renal progenitors from both locations were positive for PAX-2, CD133 and CD24 and exhibited multipotent differentiation ability. Recent studies indicated that microRNAs (miRNAs), a class of noncoding small RNAs that participate in the regulation of gene expression, may play a key role in stem cell self-renewal and differentiation. Distinct sets of miRNAs are specifically expressed in pluripotent stem cells but not in adult tissues, suggesting a role for miRNAs in stem cell self-renewal. We compared miRNA expression profiles of renal progenitors with that of renal proximal tubular cells (RPTECs) and of mesenchymal stem cells (MSC) and found distinct sets of miRNAs that were specifically expressed both in tubular and glomerular ARPCs. In particular, the miR-1915 and miR-1225-5p regulated the expression of important markers of renal progenitors, such as CD133 and PAX-2, and important genes involved in the repair mechanisms of ARPCs, such as TLR2. We demonstrated that the expression of both the renal stem cell markers CD133 and PAX-2 depends, at least in part, on lower miR-1915 levels and showed that the increase of miR-1915 levels improved capacity of ARPCs to differentiate into adipocyte-like and epithelial-like cells. Finally, we found that the low levels of miR-1225-5p were responsible for high TLR2 expression in ARPCs. Therefore, together, the miR-1915 and the miR-1225-5p seems to regulate important trait of ARPCs: the stemness and the repair capacity. Sixteen samples consisting of 5 glomerular and tubular ARPCs each, 3 MSCs, and 3 RPTECS.
2013-05-30 | E-GEOD-42391 | biostudies-arrayexpress
Project description:Background: UNC50 has long been recognized as a Golgi apparatus protein in yeast, and is involved in nicotinic receptor trafficking in Caenorhabditis elegans, but little is known about UNC50 gene function in human biology despite it being conserved from yeast to high eukaryotes. Objectives: We investigated the relation between UNC50 and human hepatocellular carcinoma (HCC) and the potential mechanisms underlying HCC development. Methods: UNC50 mRNA expression patterns in 12 HCC and adjacent non-cancerous tissues determined using northern blotting were confirmed by real-time PCR in another 44 paired tissues. Microarray experiments were used to screen for global effects of UNC50 knockdown in the Hep3B cell line, and were confirmed by real-time PCR, western blotting, flow cytometry, and tetrazolium assay in both UNC50 overexpression and knockdown Hep3B cells. Results: UNC50 expression levels were upregulated in HCC tissues in comparison with the adjacent non-cancerous tissues. UNC50 knockdown reduced mRNA levels of the downstream targets of the epidermal growth factor receptor (EGFR) pathway: cyclin D1 (CCND1), EGF, matrix metalloproteinase-7 (MMP7), aldose reductase-like 1 (AKR1B10), cell surfaceM-bM-^@M-^Sassociated mucin 1 (MUC1), and gastrin (GAST). Moreover, UNC50 influenced EGF, inducing cell cycle entry by affecting cell surface EGFR amounts. Conclusions: UNC50 is a potential oncogene that promotes HCC progression by affecting the EGFR pathway. To gain insight into the role UNC50 plays in HCC progression, we used microarray analyses to identify indirect evidence of UNC50 gene function via the knockdown strategy in Hep3B cells. Hep3B cells transfected with the shRNA expression plasmids shR-467, shR-554, shR-749, and shR-MOCK were purified with 1ug/ml puromycin, and the total RNA from each cell was extracted and analyzed with oligo microarrays.
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