scholarly journals Broad Up-Regulation of Innate Defense Factors during Acute Cholera

2007 ◽  
Vol 75 (5) ◽  
pp. 2343-2350 ◽  
Author(s):  
Carl-Fredrik Flach ◽  
Firdausi Qadri ◽  
Taufiqur R. Bhuiyan ◽  
Nur H. Alam ◽  
Eva Jennische ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Lamina Propria ◽  
Intestinal Epithelium ◽  
Defense Mechanisms ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
Duodenal Mucosa ◽  
Innate Defense ◽  
Microarray Screening

ABSTRACT We used a whole-genome microarray screening system (Affymetrix human GeneChips covering 47,000 different transcripts) to examine the gene expression in duodenal mucosa during acute cholera. Biopsies were taken from the duodenal mucosa of seven cholera patients 2 and 30 days after the onset of diarrhea, and the gene expression patterns in the acute- and convalescent-phase samples were compared pairwise. Of about 21,000 transcripts expressed in the intestinal epithelium, 29 were defined as transcripts that were up-regulated and 33 were defined as transcripts that were down-regulated during acute cholera. The majority of the up-regulated genes characterized were found to have an established or possible role in the innate defense against infections; these genes included the LPLUNC1, LF, VCC1, TCN1, CD55, SERPINA3, MMP1, MMP3, IL1B, LCN2, SOCS3, GDF15, SLPI, CXCL13, and MUC1 genes. The results of confirmative PCR correlated well with the microarray data. An immunohistochemical analysis revealed increased expression of lactoferrin in lamina propria cells and increased expression of CD55 in epithelial cells, whereas increased expression of the SERPINA3 protein (α1-antichymotrypsin) was detected in both lamina propria and epithelial cells during acute cholera. The expression pattern of CD55 and SERPINA3 in cholera toxin (CT)-stimulated Caco-2 cells was the same as the pattern found in the intestinal mucosa during acute cholera, indicating that the activation of the CD55 and SERPINA3 genes in intestinal epithelium was induced by CT. In conclusion, during acute cholera infection, innate defense mechanisms are switched on to an extent not described previously. Both direct effects of CT on the epithelial cells and changes in the lamina propria cells contribute to this up-regulation.

scholarly journals Activation of the JAK1 / STAT1 Signaling Pathway is Associated with Prdx6 Expression Levels in Human Epididymis Epithelial Cells

2021 ◽  
Author(s):  
Jianyuan Li ◽  
Hui Shi ◽  
Xiaoyu Liu ◽  
Yanwei Wang ◽  
Haiyan Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Signaling Pathway ◽  
Expression Patterns ◽  
Digital Gene Expression ◽  
Protective Role ◽  
Expression Levels ◽  
Human Epididymis ◽  
Total Antioxidant ◽  
Stat1 Signaling

Abstract I. Background: Peroxiredoxin 6 (Prdx6) is widely expressed in mammalian tissues. Our previous study demonstrated that Prdx6 was expressed in human epididymis and spermatozoa, and the protective role of Prdx6 in human spermatozoa was also reported. In this study, we demonstrate the potential role and mechanism of Prdx6 in human epididymis epithelial cells (HEECs).II. Methods and Results: Western blotting was used to measure expression levels of key proteins in the JAK / STAT signaling pathway. Digital gene expression analysis (DGE) was used to identify gene expression patterns in control HECs and in HECs after Prdx6-RNA interference (P6-RNAi). The DGE analysis identified 589 up-regulated and 314 down-regulated genes (including Prdx6) in Prdx6-RNAi (P6-RNAi) HEECs. Thirteen significantly different pathways were identified between the two groups, with the majority different expressed genes belonging to the CCL, CXCL, IL, and IFIT families. In particular, the expression levels of IL6, IL6ST, and eighteen IFN related genes were significantly increased in the condition of the down-regulated expression of Prdx6. Compared to control HEECs, the expression levels of JAK1, STAT1, phosphorylated JAK1 and STAT1 were significantly increased, while the expression levels of SOCS3 was significantly decreased in P6-RNAi HEECs. The Malondialdehyde (MDA) level and total antioxidant capacity in P6-RNAi HEECs were significantly increased and decreased compared to that of control, respectively. III. Conclusions: We speculated that knockdown of Prdx6 resulted in higher levels of ROS in HEECs, which in turn, activated the JAK1 / STAT1 signaling pathway induced by IL-6 receptor and IFN.

Spatial Transcriptomics analysis of uterine gene expression in enhancer of Zeste homolog 2 (Ezh2) conditional knockout mice

2021 ◽  
Author(s):  
Ana M Mesa ◽  
Jiude Mao ◽  
Theresa I Medrano ◽  
Nathan J Bivens ◽  
Alexander Jurkevich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Reproductive Organs ◽  
Conditional Knockout ◽  
Estrogen Signaling ◽  
Uterine Epithelial Cell ◽  
Stromal Tissue

Abstract Histone proteins undergo various modifications that alter chromatin structure, including addition of methyl groups. Enhancer of homolog 2 (EZH2), is a histone methyltransferase that methylates lysine residue 27, and thereby, suppresses gene expression. EZH2 plays integral role in the uterus and other reproductive organs. We have previously shown that conditional deletion of uterine EZH2 results in increased proliferation of luminal and glandular epithelial cells, and RNAseq analyses reveal several uterine transcriptomic changes in Ezh2 conditional (c) knockout (KO) mice that can affect estrogen signaling pathways. To pinpoint the origin of such gene expression changes, we used the recently developed spatial transcriptomics (ST) method with the hypotheses that Ezh2cKO mice would predominantly demonstrate changes in epithelial cells and/or ablation of this gene would disrupt normal epithelial/stromal gene expression patterns. Uteri were collected from ovariectomized adult WT and Ezh2cKO mice and analyzed by ST. Asb4, Cxcl14, Dio2, and Igfbp5 were increased, Sult1d1, Mt3, and Lcn2 were reduced in Ezh2cKO uterine epithelium vs. WT epithelium. For Ezh2cKO uterine stroma, differentially expressed key hub genes included Cald1, Fbln1, Myh11, Acta2, and Tagln. Conditional loss of uterine Ezh2 also appears to shift the balance of gene expression profiles in epithelial vs. stromal tissue toward uterine epithelial cell and gland development and proliferation, consistent with uterine gland hyperplasia in these mice. Current findings provide further insight into how EZH2 may selectively affect uterine epithelial and stromal compartments. Additionally, these transcriptome data might provide the mechanistic understanding and valuable biomarkers for human endometrial disorders with epigenetic underpinnings.

scholarly journals Identification of Differential Gene Expression Pattern in Lens Epithelial Cells Derived from Cataractous and Noncataractous Lenses of Shumiya Cataract Rat

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Hidetoshi Ishida ◽  
Teppei Shibata ◽  
Yuka Nakamura ◽  
Yasuhito Ishigaki ◽  
Dhirendra P. Singh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Expression Patterns ◽  
Synergetic Effect ◽  
Gene Expression Pattern ◽  
Lens Opacity ◽  
Lens Epithelial Cells ◽  
Lens Fiber ◽  
Molecular Events ◽  
Old Rats

The Shumiya cataract rat (SCR) is a model for hereditary cataract. Two-thirds of these rats develop lens opacity within 10-11 weeks. Onset of cataract is attributed to the synergetic effect of lanosterol synthase (Lss) and farnesyl-diphosphate farnesyltransferase 1 (Fdft1) mutant alleles that lead to cholesterol deficiency in the lenses, which in turn adversely affects lens biology including the growth and differentiation of lens epithelial cells (LECs). Nevertheless, the molecular events and changes in gene expression associated with the onset of lens opacity in SCR are poorly understood. In the present study, a microarray-based approach was employed to analyze comparative gene expression changes in LECs isolated from the precataractous and cataractous stages of lenses of 5-week-old SCRs. The changes in gene expression observed in microarray results in the LECs were further validated using real-time reverse transcribed quantitative PCR (RT-qPCR) in 5-, 8-, and 10-week-old SCRs. A mild posterior and cortical opacity was observed in 5-week-old rats. Expressions of approximately 100 genes, including the major intrinsic protein of the lens fiber (Mip and Aquaporin 0), deoxyribonuclease II beta (Dnase2B), heat shock protein B1 (HspB1), and crystallin γ (γCry) B, C, and F, were found to be significantly downregulated (0.07-0.5-fold) in rat LECs derived from cataract lenses compared to that in noncataractous lenses (control). Thus, our study was aimed at identifying the gene expression patterns during cataract formation in SCRs, which may be responsible for cataractogenesis in SCR. We proposed that cataracts in SCR are associated with reduced expression of these lens genes that have been reported to be related with lens fiber differentiation. Our findings may have wider implications in understanding the effect of cholesterol deficiency and the role of cholesterol-lowering therapeutics on cataractogenesis.

scholarly journals Profiling solute-carrier transporters in key metabolic tissues during the postpartum evolution of mammary epithelial cells from nonsecretory to secretory

2019 ◽  
Vol 51 (11) ◽  
pp. 539-552
Author(s):  
Osman V. Patel ◽  
Theresa Casey ◽  
Karen Plaut
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Epithelial Cells ◽  
Energy Homeostasis ◽  
Mammary Epithelial Cells ◽  
Expression Patterns ◽  
Late Pregnancy ◽  
Mammary Epithelial ◽  
Sugar Transporters ◽  
Solute Carrier

Modifications in the abundance of solute-carrier (SLC) transcripts in tandem with adjustments in genes-associated with energy homeostasis during the postpartum transition of the mammary epithelial cells (MEC) from nonsecretory to secretory is pivotal for supporting milk synthesis. The goal of this study was to identify differentially expressed SLC genes across key metabolic tissues between late pregnancy and onset of lactation. Total RNA was isolated from the mammary, liver, and adipose tissues collected from rat dams on day 20 of pregnancy (P20) and day 1 of lactation (L1) and gene expression was measured with Rat 230 2.0 Affymetrix GeneChips. LIMMA was utilized to identify the differential gene expression patterns between P20 and L1 tissues. Transcripts engaged in conveying anions, cations, carboxylates, sugars, amino acids, metals, nucleosides, vitamins, and fatty acids were significantly increased ( P < 0.05) in MEC during the P20 to L1 shift. Downregulated ( P < 0.05) genes in the mammary during the physiological transition included GLUT8 and SLC45a3. In the liver, SLC genes encoding for anion, carbonyl, and nucleotide sugar transporters were upregulated ( P < 0.05) at L1. while genes facilitating transportation of anions and hexose were increased ( P < 0.05), from P20 to L1 in the adipose tissue. GLUT1 and GLUT4 in the liver, along with GLUT4 and SGLT2 in the adipose tissue, were repressed ( P < 0.05) at L1. Our results illustrate that MEC exhibit dynamic molecular plasticity during the nonsecretory to secretory transition and increase biosynthetic capacity through a coordinated tissue specific SLC transcriptome modification to facilitate substrate transfer.

scholarly journals Involvement of Myeloid Dendritic Cells in the Development of Gastric Secondary Lymphoid Follicles in Helicobacter pylori-Infected Neonatally Thymectomized BALB/c Mice

2003 ◽  
Vol 71 (4) ◽  
pp. 2153-2162 ◽  
Author(s):  
Toshiki Nishi ◽  
Kazuichi Okazaki ◽  
Kimio Kawasaki ◽  
Toshiro Fukui ◽  
Hiroyuki Tamaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Helicobacter Pylori ◽  
Dendritic Cells ◽  
Epithelial Cells ◽  
Lamina Propria ◽  
Myeloid Dendritic Cells ◽  
Lymphoid Follicles ◽  
Inflammatory Protein ◽  
H Pylori ◽  
Antigen Presenting

ABSTRACT We previously described an animal model of Helicobacter pylori-induced follicular gastritis in neonatally thymectomized (nTx) mice. However, it is still not clear whether antigen-presenting dendritic cells (DCs) in the stomach have a role in the development of secondary follicles in H. pylori-infected nTx mice. We investigated the distribution of DC subsets using this model and examined their roles. To identify lymphoid and myeloid DCs, sections were stained with anti-CD11c (pan-DC marker) in combination with anti-CD8α (lymphoid DC marker) or anti-CD11b (myeloid DC marker) and were examined with a confocal microscope. Expression of macrophage inflammatory protein 3α (MIP-3α), which chemoattracts immature DCs, was analyzed by real-time PCR and immunohistochemistry. Follicular dendritic cells (FDCs) were stained with anti-SKY28 antibodies. In noninfected nTx mice, a few myeloid and lymphoid DCs were observed in the bottom portion of the lamina propria, whereas in H. pylori-infected nTx mice, there was an increased influx of myeloid DCs throughout the lamina propria. FDC staining was also observed in the stomachs of members of the infected group. MIP-3α gene expression was upregulated in the infected nTx group, and the immunohistochemistry analysis revealed MIP-3α-positive epithelial cells. These data suggest that H. pylori infection upregulates MIP-3α gene expression in gastric epithelial cells and induces an influx of myeloid DCs in the lamina propria of the gastric mucosa in nTx mice. Myeloid DCs and FDCs might contribute to the development of gastric secondary lymphoid follicles in H. pylori-infected nTx mice.

Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment

2003 ◽  
Vol 14 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Susan Keay ◽  
Francoise Seillier-Moiseiwitsch ◽  
Chen-Ou Zhang ◽  
Toby C. Chai ◽  
Jialu Zhang
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Interstitial Cystitis ◽  
Expression Patterns ◽  
Epithelial Cell Proliferation ◽  
Normal Cells ◽  
Bladder Epithelial Cell ◽  
Normal Bladder

Explanted bladder epithelial cells from patients with interstitial cystitis (IC) have been shown to differ from explanted control cells in several ways, including production of an antiproliferative factor (APF), altered production of certain epithelial growth factors, and rate of proliferation. To better understand the role of the APF in abnormal bladder epithelial cell proliferation in IC, we studied gene expression patterns in normal bladder epithelial cells treated with APF vs. mock APF and compared them to expression patterns in IC vs. normal cells using microarray analysis. Oligo-dT-primed total cellular RNA was labeled with [33P]dCTP and hybridized to GeneFilter GF211 microarray membranes (Research Genetics) containing cDNA for 3,964 human genes. Thirteen genes that function in epithelial cell proliferation or differentiation were consistently differentially expressed in both IC (compared with control) and APF-treated (compared with mock APF-treated) normal bladder epithelial cells. The general pattern of gene expression in IC and APF-treated cells suggested a less proliferative phenotype, with increased expression of E-cadherin, phosphoribosylpyrophosphate synthetase-associated protein 39, and SWI/SNF complex 170-kDa subunit, and decreased expression of vimentin, α2-integrin, α1-catenin, cyclin D1, and jun N-terminal kinase 1; these findings were confirmed for the structural gene products (E-cadherin, vimentin, α2-integrin, and α-catenin) by immunohistochemistry. These results are compatible with the previously noted decreased proliferation rate of IC and APF-treated normal cells, and indicate that the mechanism whereby APF inhibits cell proliferation may involve both downregulation of genes that stimulate cell proliferation along with upregulation of genes that inhibit cell growth.

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