scholarly journals Altered gene expression in slc4a11−/− mouse cornea highlights SLC4A11 roles

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Bernardo V. Alvarez ◽  
Marilyse Piché ◽  
Carolin Aizouki ◽  
Fariha Rahman ◽  
Jonathan M. J. Derry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Energy Metabolism ◽  
Cell Fate ◽  
Ion Homeostasis ◽  
Corneal Dystrophy ◽  
Mrna Levels ◽  
Altered Expression ◽  
Reverse Transcription Pcr ◽  
Extracellular Region

AbstractSLC4A11 is a H+/NH3/water transport protein, of corneal endothelial cells. SLC4A11 mutations cause congenital hereditary endothelial dystrophy and some cases of Fuchs endothelial corneal dystrophy. To probe SLC4A11’s roles, we compared gene expression in RNA from corneas of 17-week-old slc4a11−/− (n = 3) and slc4a11+/+ mice (n = 3) and subjected to RNA sequencing. mRNA levels for a subset of genes were also assessed by quantitative real-time reverse transcription PCR (qRT RT-PCR). Cornea expressed 13,173 genes, which were rank-ordered for their abundance. In slc4a11−/− corneas, 100 genes had significantly altered expression. Abundant slc14a1 expression, encoding the urea transporter UT-A, suggests a significant role in the cornea. The set of genes with altered expression was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, revealing that alterations clustered into extracellular region, cytoskeleton, cell adhesion and plasma membrane functions. Gene expression changes further clustered into classes (with decreasing numbers of genes): cell fate and development, extracellular matrix and cell adhesion, cytoskeleton, ion homeostasis and energy metabolism. Together these gene changes confirm earlier suggestions of a role of SLC4A11 in ion homeostasis, energy metabolism, cell adhesion, and reveal an unrecognized SLC4A11 role in cytoskeletal organization.

scholarly journals Persistent Changes in Gene Expression Induced by Estrogen and Progesterone in the Rat Mammary Gland

2001 ◽  
Vol 15 (11) ◽  
pp. 1993-2009 ◽  
Author(s):  
Melanie R. Ginger ◽  
Maria F. Gonzalez-Rimbau ◽  
Jason P. Gay ◽  
Jeffrey M. Rosen
Keyword(s):  
Gene Expression ◽  
Mammary Gland ◽  
Cell Fate ◽  
Noncoding Rna ◽  
Previous Treatment ◽  
Hormone Treatment ◽  
Subtractive Hybridization ◽  
Epidemiological Studies ◽  
Altered Expression ◽  
Hormonal Milieu

Abstract Epidemiological studies have consistently shown that an early full-term pregnancy is protective against breast cancer. We hypothesize that the hormonal milieu that is present during pregnancy results in persistent changes in the pattern of gene expression in the mammary gland, leading to permanent changes in cell fate that determine the subsequent proliferative response of the gland. To investigate this hypothesis, we have used suppression subtractive hybridization to identify genes that are persistently up-regulated in the glands of E- and progesterone (P)-treated Wistar-Furth rats 28 d after steroid hormone treatment compared with age-matched virgins. Using this approach, a number of genes displaying persistent altered expression in response to previous treatment with E and P were identified. Two markers have been characterized in greater detail: RbAp46 and a novel gene that specifies a noncoding RNA (designated G.B7). Both were persistently up-regulated in the lobules of the regressed gland and required previous treatment with both E and P for maximal persistent expression. RbAp46 has been implicated in a number of complexes involving chromatin remodeling, suggesting a mechanism whereby epigenetic factors responsible for persistent changes in gene expression may be related to the determination of cell fate. These results provide the first support at the molecular level for the hypothesis that hormone-induced persistent changes in gene expression are present in the involuted mammary gland.

53 Pre-implantation exposure to bisphenol A and 4-tert-octylphenol result in disruption of calcium channels

2019 ◽  
Vol 31 (1) ◽  
pp. 152
Author(s):  
D. N. Tran ◽  
J.-H. Lee ◽  
Y.-M. Yoo ◽  
E.-M. Jung ◽  
C. Ahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bisphenol A ◽  
Calcium Transport ◽  
Oestrogen Receptor ◽  
Implantation Site ◽  
Vehicle Group ◽  
Mrna Levels ◽  
Implantation Failure ◽  
Transport Channel ◽  
Altered Expression

Miscarriage due to blastocyst implantation failure occurs in up to two-thirds of all miscarriage cases in humans. Calcium (Ca2+) has been shown to involve many cellular signal transduction pathways as well as regulation of cell adhesion, which is necessary for the physiology process of endometrial epithelial cell transformation and stromal cell decidualization during embryo implantation. Exposure to endocrine-disrupting chemicals (ED) can regulate the expression of genes associated with calcium transport in during pregnancy such as TRPV5, TRPV6, PMCA, and NCX1. Additionally, exposure to ED during early gestation results in disrupted intrauterine implantation, uterine receptive, leading to implantation failure. In this study, oestrogen (E2), bisphenol A (BPA), octylphenol (OP), and/or ICI 182,780 (oestrogen receptor antagonist, ICI) were injected subcutaneously from gestation Day 1 to gestation Day 3 post coitus. The number of implantation sites was significantly lower in the OP group, and no implantation site was observed in the E2 and ED+ICI groups. There were differences in the expression of calcium transient transport channel between maternal uterine and implantation. The level of TRPV6 and TRPV5 mRNA and protein was significantly increased by ED and/or ICI treatment in the uterus. The levels of TRPV5 and TRPV6 gene expression were significantly increased by ED with/without ICI treatment in the uterus. However, TRPV5 and TRPV6 gene expression was significantly lower in implantation site samples. The NCX1 and PMCA1 mRNA levels were significantly decreased by OP and BPA in the implantation site samples. Both mRNA and protein levels of MUC1 were markedly higher in all groups, except the BPA group when compared with the vehicle group in the uterus. The LIF and HOXA-10 mRNA were significantly low in E2; BPA+ICI; OP; and/or ICI in both the uterus and implantation site. Expression of the oestrogen receptor (ERa) and progesterone receptor (PR) was significantly lower in all groups except the BPA group when compared with the vehicle group. Taken together, E2, BPA, and OP disrupt the success of implantation through altered expression of calcium transport genes.

Alternative splicing in plants

2008 ◽  
Vol 36 (3) ◽  
pp. 508-510 ◽  
Author(s):  
Craig G. Simpson ◽  
Dominika Lewandowska ◽  
John Fuller ◽  
Monika Maronova ◽  
Maria Kalyna ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Reverse Transcription ◽  
Protein Function ◽  
Mrna Levels ◽  
Reverse Transcription Pcr ◽  
Multiple Genes ◽  
The Impact

The impact of AS (alternative splicing) is well-recognized in animal systems as a key regulator of gene expression and proteome complexity. In plants, AS is of growing importance as more genes are found to undergo AS, but relatively little is known about the factors regulating AS or the consequences of AS on mRNA levels and protein function. We have established an accurate and reproducible RT (reverse transcription)–PCR system to analyse AS in multiple genes. Initial studies have identified new AS events confirming that current values for the frequency of AS in plants are likely to be underestimates.

Oxidoreductase, morphogenesis, extracellular matrix, and calcium ion-binding gene expression in streptozotocin-induced diabetic rat heart

2007 ◽  
Vol 293 (3) ◽  
pp. E759-E768 ◽  
Author(s):  
Erik van Lunteren ◽  
Michelle Moyer
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Calcium Ion ◽  
Ion Homeostasis ◽  
Fold Change ◽  
Diabetic Rat ◽  
Ion Binding ◽  
Oxidoreductase Activity ◽  
Altered Expression ◽  
Calcium Ion Binding

Diabetes has far-ranging effects on cardiac structure and function. Previous gene expression studies of the heart in animal models of type 1 diabetes concur that there is altered expression of genes involved in lipid and protein metabolism, but they diverge with regard to expression changes involving many other functional groups of genes of mechanistic importance in diabetes-induced cardiac dysfunction. To obtain additional information about these controversial areas, genome-wide expression was assessed using microarrays in left ventricle from streptozotocin-diabetic and normal rats. There were 261 genes with statistically significant altered expression of at least ±1.5-fold, of which 124 were increased and 137 reduced by diabetes. Gene ontology assignment testing identified several statistical significantly overrepresented groups among genes with altered expression, which differed for increased compared with reduced expression. Relevant gene groups with increased expression by diabetes included lipid metabolism ( P < 0.001, n = 13 genes, fold change 1.5 to 14.6) and oxidoreductase activity ( P < 0.001, n = 17, fold change 1.5 to 4.6). Groups with reduced expression by diabetes included morphogenesis ( P < 0.00001, n = 28, fold change −1.5 to −5.1), extracellular matrix ( P < 0.02, n = 9, fold change −1.5 to −3.9), cell adhesion ( P < 0.05, n = 10, fold change −1.5 to −2.7), and calcium ion binding ( P < 0.01, n = 13, fold change −1.5 to −3.0). Array findings were verified by quantitative PCR for 36 genes. These data combined with previous findings strengthen the evidence for diabetes-induced cardiac gene expression changes involved in cell growth and development, oxidoreductase activity, and the extracellular matrix and also point out other gene groups not previously identified as being affected, such as those involved in calcium ion homeostasis.

scholarly journals <i>In Vitro</i> Exposure to Isoprene-Derived Secondary Organic Aerosol by Direct Deposition and its Effects on <i>COX-2</i> and <i>IL-8</i> Gene Expression

2016 ◽  
Author(s):  
Maiko Arashiro ◽  
Ying-Hsuan Lin ◽  
Kenneth G. Sexton ◽  
Zhenfa Zhang ◽  
Ilona Jaspers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Secondary Organic Aerosol ◽  
Organic Aerosol ◽  
Mrna Levels ◽  
Altered Expression ◽  
Direct Deposition ◽  
Discovery Research ◽  
Human Lung Cells ◽  
Cox 2

Abstract. Atmospheric oxidation of isoprene, the most abundant non-methane hydrocarbon emitted into Earth’s atmosphere primarily from terrestrial vegetation, is now recognized as a major contributor to the global secondary organic aerosol (SOA) burden. Anthropogenic pollutants significantly enhance isoprene SOA formation through acid-catalyzed heterogeneous chemistry of epoxide products. Since isoprene SOA formation as a source of fine aerosol is a relatively recent discovery, research is lacking on evaluating its potential adverse effects on human health. The objective of this study was to examine the effect of isoprene-derived SOA on inflammation-associated gene expression in human lung cells using a direct deposition exposure method. We assessed altered expression of inflammation-related genes in human bronchial epithelial cells (BEAS-2B) exposed to isoprene-derived SOA generated in an outdoor chamber facility. Measurements of gene expression of known inflammatory biomarkers interleukin 8 (IL-8) and cyclooxygenase 2 (COX-2) in exposed cells, together with complementary chemical measurements, showed that a dose of 0.067 µg cm−2 of SOA from isoprene photooxidation leads to statistically significant increases in IL-8 and COX-2 mRNA levels. Resuspension exposures using aerosol filter extracts corroborated these findings, supporting the conclusion that isoprene-derived SOA constituents induce the observed changes in mRNA levels. Future studies are needed to systematically examine the molecular mechanisms of toxicity.

Altered expression of cell adhesion genes and hybrid male sterility between subspecies ofDrosophila pseudoobscura

Genome ◽  
2019 ◽  
Vol 62 (10) ◽  
pp. 657-663 ◽  
Author(s):  
Alwyn Go ◽  
Doaa Alhazmi ◽  
Alberto Civetta
Keyword(s):  
Gene Expression ◽  
Cell Adhesion ◽  
Male Sterility ◽  
Drosophila Pseudoobscura ◽  
Hybrid Male ◽  
Hybrid Male Sterility ◽  
Altered Expression ◽  
A Genome ◽  
Hybrid Genome ◽  
A Cell

Drosophila pseudoobscura pseudoobscura and Drosophila pseudoobscura bogotana are two closely related subspecies with incomplete reproductive isolation. A genome-wide comparison of expression in hybrids relative to parental subspecies has been previously used to identify genes with significant changes in expression uniquely associated with the sterile condition. The misexpression (i.e., gene expression beyond levels found in parentals) of such genes could be directly linked to the onset of sterility or could alternatively be caused by incompatibilities in a hybrid genome without a direct link to sterility. Cell adhesion was previously found to be one of the largest gene ontologies with changes in expression linked to sterility. Here we used gene expression assays in fertile backcross male progeny, along with introgression progeny in which we swap a major hybrid male sterility (HMS) allele, to generate fertile and sterile males genotypically similar to F1sterile hybrids. We identify a cell adhesion gene (GA10921) whose change in expression is directly linked to sterility and modulated by a previously characterized HMS protein. GA10921 adds to our rather limited knowledge of changes in gene expression associated with HMS, and to the identification of gene interacting partners linked to HMS.

scholarly journals Identification of the growth hormone receptor in an advanced teleost, the tilapia (Oreochromis mossambicus) with special reference to its distinct expression pattern in the ovary

2004 ◽  
Vol 181 (1) ◽  
pp. 65-76 ◽  
Author(s):  
S Kajimura ◽  
N Kawaguchi ◽  
T Kaneko ◽  
I Kawazoe ◽  
T Hirano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Hormone Receptor ◽  
Oreochromis Mossambicus ◽  
Mrna Levels ◽  
Female Reproduction ◽  
Immature Oocytes ◽  
Putative Signal Peptide ◽  
Isolation And Characterization ◽  
Extracellular Region ◽  
Igf I

There is considerable evidence that the GH/IGF-I axis plays an important role in female reproduction. We report the isolation and characterization of the GH receptor (GH-R) and its gene expression profile during oogenesis in the tilapia, Oreochromis mossambicus. cDNA encoding GH-R was cloned and sequenced from the tilapia liver. The predicted GH-R preprotein consisted of 635 amino acids and contained a putative signal peptide, an extracellular region with a characteristic motif, a single transmembrane region, and a cytoplasmic region with conserved box 1 and 2 domains. The tilapia GH-R shared 34-74% identities with known GH-Rs in vertebrates. A binding assay using COS-7 cells showed that the cloned GH-R bound specifically to tilapia GH. Northern blot analysis showed a single mRNA transcript in the liver and ovary. In situ hybridization revealed intense signals of GH-R in the cytoplasm and nucleus of immature oocytes. The granulosa and theca cells surrounding vitellogenic oocytes also contained the GH-R mRNA signals. About a tenfold greater level of GH-R mRNA was found in the immature oocytes versus the mature oocytes, along with high levels of IGF-I mRNA. There were no significant changes in mRNA levels of GH-R and IGF-I in the liver or in plasma IGF-I levels during oocyte development. No correlation was found between hepatic GH-R mRNA and ovarian GH-R mRNA. These results suggest that the GH/IGF-I axis in the ovary may be involved in the early phases of oogenesis, under a different regulatory mechanism of GH-R gene expression from that of the liver.

scholarly journals Transforming growth factor-β signaling in hypertensive remodeling of porcine aorta

2009 ◽  
Vol 297 (6) ◽  
pp. H2044-H2053 ◽  
Author(s):  
Natasa Popovic ◽  
Eric A. Bridenbaugh ◽  
Jessemy D. Neiger ◽  
Jin-Jia Hu ◽  
Marina Vannucci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Vascular Remodeling ◽  
Transforming Growth Factor ◽  
Regulation Of Gene Expression ◽  
Transforming Growth Factor Β ◽  
Altered Expression ◽  
Protein Levels ◽  
Extracellular Region

A porcine aortic coarctation model was used to examine regulation of gene expression in early hypertensive vascular remodeling. Aortic segments were collected proximal (high pressure) and distal (low pressure) to the coarctation after 2 wk of sustained hypertension (mean arterial pressure > 150 mmHg). Porcine 10K oligoarrays used for gene expression profiling of the two regions of aorta revealed downregulation of cytoskeletal and upregulation of extracellular region genes relative to the whole genome. A genomic database search for transforming growth factor-β (TGF-β) control elements showed that 19% of the genes that changed expression due to hypertension contained putative TGF-β control elements. Real-time RT-PCR and microarray analysis showed no change in expression of TGF-β1, TGF-β2, TGF-β3, or bone morphogenetic proteins-2 and -4, yet immunohistochemical staining for phosphorylated SMAD2, an indicator of TGF-β signaling, and for phosphorylated SMAD1/5/8, an indicator of signaling through the bone morphogenetic proteins, showed the highest percentage of positively stained cells in the proximal aortic segments of occluded animals. For TGF-β signaling, this increase was significantly different than for sham-operated controls. Western blot analysis showed no difference in total TGF-β1 protein levels with respect to treatment or aortic segment. Immunohistochemistry showed that the protein levels of latency-associated peptide was decreased in proximal segments of occluded animals. Collectively, these results suggest that activation of TGF-β, but not altered expression, may be a major mechanism regulating early hypertensive vascular remodeling.

scholarly journals Genetics of trans-regulatory variation in gene expression

2017 ◽  
Author(s):  
Frank W. Albert ◽  
Joshua S. Bloom ◽  
Jake Siegel ◽  
Laura Day ◽  
Leonid Kruglyak
Keyword(s):  
Gene Expression ◽  
Statistical Power ◽  
Target Genes ◽  
Transcriptome Profiling ◽  
Mrna Levels ◽  
Heritable Variation ◽  
Altered Expression ◽  
Regulatory Variation ◽  
Transcription Factor Genes ◽  
Transcriptome Variation

AbstractHeritable variation in gene expression provides a critical bridge between differences in genome sequence and the biology of many traits, including common human diseases. However, the sources of most regulatory genetic variation remain unknown. Here, we used transcriptome profiling in 1,012 yeast segregants to map the genetic basis of variation in gene expression with high statistical power. We identified expression quantitative trait loci (eQTL) that together account for over 70% of the total genetic contribution to variation in mRNA levels, allowing us to examine the sources of regulatory variation comprehensively. We found that variation in the expression of a typical gene has a complex genetic architecture involving multiple eQTL. We also detected hundreds of eQTL pairs with significant non-additive interactions in an unbiased genome-wide scan. Although most genes were influenced by a local eQTL located close to the gene, most expression variation arose from distant, trans-acting eQTL located far from their target genes. Nearly all distant eQTL clustered at 102 “hotspot” locations, some of which influenced the expression of thousands of genes. Hotspot regions were enriched for transcription factor genes and altered expression of their target genes though both direct and indirect mechanisms. Many local eQTL had no detectable effects on the expression of other genes in trans. These results reveal the complexity of genetic influences on transcriptome variation in unprecedented depth and detail.

Abstract 438: Global Gene Expression Analysis of Human Perivascular Adipocytes Reveals Reduced Expression of Insulin and Wnt Signaling Genes: Implications for Inflammatory Crosstalk

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Tapan K Chatterjee ◽  
David G Kuhel ◽  
David Y Hui ◽  
Neal L Weintraub
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Human Subjects ◽  
Adipogenic Differentiation ◽  
Expression Patterns ◽  
Mrna Levels ◽  
Altered Expression

Inflammatory crosstalk between PV adipose tissue and the blood vessel wall has been proposed to contribute to the pathogenesis of atherosclerosis. We reported that PV adipocytes exhibit a pro-inflammatory phenotype, reduced state of differentiation, and altered expression of developmental genes as compared with subcutaneous (SQ) adipocytes derived from the same human subjects. To define global differences in gene expression patterns between PV and SQ adipocytes, genome-wide microarray studies were performed in three sets of in vitro differentiated SQ and PV adipocytes derived from unrelated human subjects. Insulin-regulated and Wnt signaling genes were markedly down-regulated in PV adipocytes. Validation of microarray data by qPCR demonstrated reductions in expression of C/EBPα, PPARγ, FABP4, adiponectin, lipoprotein lipase, hormone sensitive lipase and perilipin in PV compared to SQ adipocytes. We further observed that insulin-induced Akt ser-473 phosphorylation and glucose uptake were markedly reduced (∼ 3 fold and 4 fold, respectively) in differentiated PV adipocytes compared to SQ adipocytes. The mRNA levels of insulin and insulin-like growth factor receptors, however, were similar in adipocytes differentiated from these two depots. Regarding the Wnt pathway, PV adipocytes exhibited dramatically elevated expression of Wnt inhibitor DKK1 (2864%) and reduced expression of Wnt 5A (50%), FDZ4 (38%), and LRP5 (38%). Further evaluation revealed that these Wnt signaling pathway genes, like those of the insulin signaling pathway, correlated with the extent of adipogenic differentiation. We propose that dysregulation of Wnt 5A/FDZ4 and insulin signaling pathways contributes to impaired adipogenic differentiation and insulin resistance in PV adipocytes. This, in turn, may contribute to heightened inflammatory crosstalk between PV adipose tissue and the vascular wall in the setting of atherosclerosis.

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