ACE INHIBITION ATTENUATES RENAL PDGF GENE EXPRESSION AND CELL PROLIFERATION IN SUBTOTAL NEPHRECTOMY

AbstractBackgroundStaufen2 (STAU2) is an RNA binding protein involved in the posttranscriptional regulation of gene expression. In neurons, STAU2 is required to maintain the balance between differentiation and proliferation of neural stem cells through asymmetric cell division. However, the importance of controlling STAU2 expression for cell cycle progression is not clear in non-neuronal dividing cells. We recently showed that STAU2 transcription is inhibited in response to DNA-damage due to E2F1 displacement from theSTAU2gene promoter. We now study the regulation of STAU2 steady-state levels in unstressed cells and its consequence for cell proliferation.ResultsCRISPR/Cas9-mediated and RNAi-dependent STAU2 depletion in the non-transformed hTERT-RPE1 cells both facilitate cell proliferation suggesting that STAU2 expression influences pathway(s) linked to cell cycle controls. Such effects are not observed in the CRISPR STAU2-KO cancer HCT116 cells nor in the STAU2-RNAi-depleted HeLa cells. Interestingly, a physiological decrease in the steady-state level of STAU2 is controlled by caspases. This effect of peptidases is counterbalanced by the activity of the CHK1 pathway suggesting that STAU2 partial degradation/stabilization fines tune cell cycle progression in unstressed cells. A large-scale proteomic analysis using STAU2/biotinylase fusion protein identifies known STAU2 interactors involved in RNA translation, localization, splicing, or decay confirming the role of STAU2 in the posttranscriptional regulation of gene expression. In addition, several proteins found in the nucleolus, including proteins of the ribosome biogenesis pathway and of the DNA damage response, are found in close proximity to STAU2. Strikingly, many of these proteins are linked to the kinase CHK1 pathway, reinforcing the link between STAU2 functions and the CHK1 pathway. Indeed, inhibition of the CHK1 pathway for 4 h dissociates STAU2 from proteins involved in translation and RNA metabolism.ConclusionsThese results indicate that STAU2 is involved in pathway(s) that control(s) cell proliferation, likely via mechanisms of posttranscriptional regulation, ribonucleoprotein complex assembly, genome integrity and/or checkpoint controls. The mechanism by which STAU2 regulates cell growth likely involves caspases and the kinase CHK1 pathway.

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The Potential of 2-aza-8-Oxohypoxanthine as a Cosmetic Ingredient

Cosmetics ◽

10.3390/cosmetics8030060 ◽

2021 ◽

Vol 8 (3) ◽

pp. 60

Author(s):

Hisae Aoshima ◽

Masayuki Ito ◽

Rinta Ibuki ◽

Hirokazu Kawagishi

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Microarray Analysis ◽

Dna Microarray ◽

Cell Activation ◽

Skin Barrier ◽

Efficacy Evaluation ◽

Activation Effect ◽

Expression Levels ◽

Dna Microarray Analysis

In this study, we verified the effects of 2-aza-8-oxohypoxanthine (AOH) on human epidermal cell proliferation by performing DNA microarray analysis. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, which measures mitochondrial respiration in normal human epidermal keratinocyte (NHEK) cells. Gene expression levels were determined by DNA microarray analysis of 177 genes involved in skin aging and disease. AOH showed a significant increase in cell viability at concentrations between 7.8 and 31.3 μg/mL and a significant decrease at concentrations above 250 μg/mL. DNA microarray analysis showed that AOH significantly increased the gene expression of CLDN1, DSC1, DSG1, and CDH1 (E-cadherin), which are involved in intercellular adhesion and skin barrier functioning. AOH also up-regulated the expression of KLK5, KLK7, and SPIMK5, which are proteases involved in stratum corneum detachment. Furthermore, AOH significantly stimulated the expression of KRT1, KRT10, TGM1, and IVL, which are considered general differentiation indicators, and that of SPRR1B, a cornified envelope component protein. AOH exerted a cell activation effect on human epidermal cells. Since AOH did not cause cytotoxicity, it was considered that the compound had no adverse effects on the skin. In addition, it was found that AOH stimulated the expression levels of genes involved in skin barrier functioning by DNA microarray analysis. Therefore, AOH has the potential for practical use as a cosmetic ingredient. This is the first report of efficacy evaluation tests performed for AOH.

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Biological effects of tourmaline treatment on Dehalococcoides spp. during the reductive dechlorination of trichloroethylene

RSC Advances ◽

10.1039/d0ra10830h ◽

2021 ◽

Vol 11 (20) ◽

pp. 12086-12094

Author(s):

Tielong Li ◽

Jiaxin Wen ◽

Bingjie Li ◽

Shihu Ding ◽

Wei Wang

Keyword(s):

Gene Expression ◽

Cell Proliferation ◽

Community Structure ◽

Reductive Dechlorination ◽

Biological Effects ◽

Dechlorinating Bacteria ◽

Contaminated Aquifers ◽

Tce Degradation ◽

Induced Changes

To explore the application of mineral in bioremediation of contaminated aquifers, this study investigated tourmaline-induced changes in TCE degradation, community structure, cell proliferation and gene expression of dechlorinating bacteria.

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Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue

Endocrine Related Cancer ◽

10.1677/erc.1.01165 ◽

2006 ◽

Vol 13 (2) ◽

pp. 617-628 ◽

Cited By ~ 51

Author(s):

C L Wilson ◽

A H Sims ◽

A Howell ◽

C J Miller ◽

R B Clarke

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cell Proliferation ◽

Breast Tissue ◽

Epithelial Cell Proliferation ◽

Human Breast ◽

Human Breast Tissue ◽

Tissue Microenvironment ◽

Normal Human Breast ◽

Normal Human

Oestrogen (E) is essential for normal and cancer development in the breast, while anti-oestrogens have been shown to reduce the risk of the disease. However, little is known about the effect of E on gene expression in the normal human breast, particularly when the epithelium and stroma are intact. Previous expression profiles of the response to E have been performed on tumour cell lines, in the absence of stroma. We investigated gene expression in normal human breast tissue transplanted into 9–10-week-old female athymic nude (Balb/c nu/nu) mice. After 2 weeks, when epithelial proliferation is minimal, one-third of the mice were treated with 17β-oestradiol (E2) to give human luteal-phase levels in the mouse, which we have previously shown to induce maximal epithelial cell proliferation. RNA was isolated from treated and untreated mice, labelled and hybridized to Affymetrix HG-U133A (human) GeneChips. Gene expression levels were generated using BioConductor implementations of the RMA and MAS5 algorithms. E2 treatment was found to represent the largest source of variation in gene expression and cross-species hybridization of mouse RNA from xenograft samples was demonstrated to be negligible. Known E2-responsive genes (such as TFF1 and AREG), and genes thought to be involved in breast cancer metastasis (including mammoglobin, KRT19 and AGR2), were upregulated in response to E treatment. Genes known to be co-expressed with E receptor α in breast cancer cell lines and tumours were both upregulated (XBP-1 and GREB1) and downregulated (RARRES1 and GATA3). In addition, genes that are normally expressed in the myoepithelium and extracellular matrix that maintain the tissue microenvironment were also differentially expressed. This suggests that the response to oestrogen in normal breast is highly dependent upon epithelial–stromal/myoepithelial interactions which maintain the tissue microenvironment during epithelial cell proliferation.

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Iodide- and Glucose-Handling Gene Expression Regulated by Sorafenib or Cabozantinib in Papillary Thyroid Cancer

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-3023 ◽

2015 ◽

Vol 100 (5) ◽

pp. 1771-1779 ◽

Cited By ~ 10

Author(s):

Maomei Ruan ◽

Min Liu ◽

Qianggang Dong ◽

Libo Chen

Keyword(s):

Gene Expression ◽

Cell Cycle ◽

Signal Transduction ◽

Cell Proliferation ◽

Thyroid Cancer ◽

Western Blot ◽

Glucose Transporter ◽

Signal Transduction Pathways ◽

Papillary Thyroid ◽

Cycle Arrest

Abstract Context: The aberrant silencing of iodide-handling genes accompanied by up-regulation of glucose metabolism presents a major challenge for radioiodine treatment of papillary thyroid cancer (PTC). Objective: This study aimed to evaluate the effect of tyrosine kinase inhibitors on iodide-handling and glucose-handling gene expression in BHP 2-7 cells harboring RET/PTC1 rearrangement. Main Outcome Measures: In this in vitro study, the effects of sorafenib or cabozantinib on cell growth, cycles, and apoptosis were investigated by cell proliferation assay, cell cycle analysis, and Annexin V-FITC apoptosis assay, respectively. The effect of both agents on signal transduction pathways was evaluated using the Western blot. Quantitative real-time PCR, Western blot, immunofluorescence, and radioisotope uptake assays were used to assess iodide-handling and glucose-handling gene expression. Results: Both compounds inhibited cell proliferation in a time-dependent and dose-dependent manner and caused cell cycle arrest in the G0/G1 phase. Sorafenib blocked RET, AKT, and ERK1/2 phosphorylation, whereas cabozantinib blocked RET and AKT phosphorylation. The restoration of iodide-handling gene expression and inhibition of glucose transporter 1 and 3 expression could be induced by either drug. The robust expression of sodium/iodide symporter induced by either agent was confirmed, and 125I uptake was correspondingly enhanced. 18F-fluorodeoxyglucose accumulation was significantly decreased after treatment by either sorafenib or cabozantinib. Conclusions: Sorafenib and cabozantinib had marked effects on cell proliferation, cell cycle arrest, and signal transduction pathways in PTC cells harboring RET/PTC1 rearrangement. Both agents could be potentially used to enhance the expression of iodide-handling genes and inhibit the expression of glucose transporter genes.

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