scholarly journals The Caenorhabditis elegans APC-related gene apr-1 is required for epithelial cell migration and Hox gene expression

2000 ◽  
Vol 14 (7) ◽  
pp. 874-886 ◽  
Author(s):  
Erika Fröhli Hoier ◽  
William A. Mohler ◽  
Stuart K. Kim ◽  
Alex Hajnal
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Precursor Cells ◽  
Related Gene ◽  
Hox Gene ◽  
Epithelial Cell Migration ◽  
Vulval Precursor Cells ◽  
Related Proteins

Inactivation of the Caenorhabditis elegans APC-related gene (apr-1) has pointed at two separate functions of apr-1. First, apr-1 is required for the migration of epithelial cells during morphogenesis of the embryo. In this process, APR-1 may act in a Cadherin/α-Catenin/β-Catenin complex as a component of adherens junctions. Second, apr-1 is required for Hox gene expression, most likely by positively regulating the activity of the Wingless signaling pathway. During embryogenesis, apr-1 is required for the expression ofceh-13 labial in anterior seam and muscle cells and during larval development, apr-1 is necessary for the expression of lin-39 deformed in the vulval precursor cells. Thus, APR-1 may positively regulate the activity of the β-Catenin/Armadillo-related proteins HMP-2 in migrating epithelial cells and BAR-1 in the vulval precursor cells.

scholarly journals A Dual Role for Oncostatin M Signaling in the Differentiation and Death of Mammary Epithelial Cells in Vivo

2008 ◽  
Vol 22 (12) ◽  
pp. 2677-2688 ◽  
Author(s):  
Paul G. Tiffen ◽  
Nader Omidvar ◽  
Nuria Marquez-Almuina ◽  
Dawn Croston ◽  
Christine J. Watson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Oncostatin M ◽  
Specific Gene ◽  
Mammary Involution

Abstract Recent studies in breast cancer cell lines have shown that oncostatin M (OSM) not only inhibits proliferation but also promotes cell detachment and enhances cell motility. In this study, we have looked at the role of OSM signaling in nontransformed mouse mammary epithelial cells in vitro using the KIM-2 mammary epithelial cell line and in vivo using OSM receptor (OSMR)-deficient mice. OSM and its receptor were up-regulated approximately 2 d after the onset of postlactational mammary regression, in response to leukemia inhibitory factor (LIF)-induced signal transducer and activator of transcription-3 (STAT3). This resulted in sustained STAT3 activity, increased epithelial apoptosis, and enhanced clearance of epithelial structures during the remodeling phase of mammary involution. Concurrently, OSM signaling precipitated the dephosphorylation of STAT5 and repressed expression of the milk protein genes β-casein and whey acidic protein (WAP). Similarly, during pregnancy, OSM signaling suppressed β-casein and WAP gene expression. In vitro, OSM but not LIF persistently down-regulated phosphorylated (p)-STAT5, even in the continued presence of prolactin. OSM also promoted the expression of metalloproteinases MMP3, MMP12, and MMP14, which, in vitro, were responsible for OSM-specific apoptosis. Thus, the sequential activation of IL-6-related cytokines during mammary involution culminates in an OSM-dependent repression of epithelial-specific gene expression and the potentiation of epithelial cell extinction mediated, at least in part, by the reciprocal regulation of p-STAT5 and p-STAT3.

Concurrence between the gene expression pattern of Actinobacillus actinomycetemcomitans in localized aggressive periodontitis and in human epithelial cells

2005 ◽  
Vol 54 (5) ◽  
pp. 497-504 ◽  
Author(s):  
Joseph Richardson ◽  
Justin Corey Craighead ◽  
Sam Linsen Cao ◽  
Martin Handfield
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Expression Pattern ◽  
Gene Expression Pattern ◽  
Aggressive Periodontitis ◽  
Actinobacillus Actinomycetemcomitans ◽  
Bacterial Gene ◽  
Bacterial Gene Expression

Actinobacillus actinomycetemcomitans is a facultatively intracellular pathogen and the aetiological agent of localized aggressive periodontitis. Screening of the genome of A. actinomycetemcomitans for in vivo-induced antigen determinants previously demonstrated that the proteome of this organism differs in laboratory culture compared with conditions found during active infection. The aim of the present study was to determine whether the bacterial gene expression pattern inferred with in vivo-induced antigen technology (IVIAT) in human infections was consistent with the gene expression pattern occurring upon epithelial cell association. To this end, a real-time PCR method was developed and used to quantify absolute and relative bacterial gene expression of A. actinomycetemcomitans grown extra- and intracellularly in two human epithelial cell lines (HeLa and IHGK). The amount of template used in the assay was normalized using the total count of viable bacteria (c.f.u.) as a reference point and performed in duplicate in at least two independent experiments. Controls for this experiment included 16S rRNA and gapdh. Transcription of all eight ORFs tested increased significantly (P < 0.05) in HeLa and IHGK cells compared with bacteria grown extracellularly. The concurrence of gene expression patterns found in the two models suggests that these epithelial cells are valid in vitro models of infection for the genes tested. IVIAT is an experimental platform that can be used as a validation tool to assess the reliability of animal and other models of infection and is applicable to most pathogens.

TLR2-mediated innate immune priming boosts lung anti-viral immunity

2020 ◽  
pp. 2001584
Author(s):  
Jason Girkin ◽  
Su-Ling Loo ◽  
Camille Esneau ◽  
Steven Maltby ◽  
Francesca Mercuri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Innate Immunity ◽  
Viral Load ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Immune Cell ◽  
Innate Immune ◽  
Immune Priming ◽  
Tlr2 Activation

Research questionAssessment of whether TLR2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases.MethodsWe employed treatment with a novel TLR2 agonist (INNA-X) prior to rhinovirus infection in mice, and INNA-X treatment in differentiated human bronchial epithelial cells derived from asthmatic-donors. We assessed viral load, immune cell recruitment, cytokines, type I and III IFN production, as well as the lung tissue and epithelial cell immune transcriptome.ResultsWe show in vivo, that a single INNA-X treatment induced innate immune priming characterised by low-level IFN-λ, Fas ligand, chemokine expression and airway lymphocyte recruitment. Treatment 7-days before infection significantly reduced lung viral load, increased IFN-β/λ expression and inhibited neutrophilic inflammation. Corticosteroid treatment enhanced the anti-inflammatory effects of INNA-X. Treatment 1-day before infection increased expression of 190 lung tissue immune genes. This tissue gene expression signature was absent with INNA-X treatment 7-days before infection, suggesting an alternate mechanism, potentially via establishment of immune cell-mediated mucosal innate immunity. In vitro, INNA-X treatment induced a priming response defined by upregulated IFN-λ, chemokine and anti-microbial gene expression that preceded an accelerated response to infection enriched for NF-κB-regulated genes and reduced viral loads, even in epithelial cells derived from asthmatic donors with intrinsic delayed anti-viral immune response.ConclusionAirway epithelial cell TLR2 activation induces prolonged innate immune priming, defined by early NF-κB activation, IFN-λ expression and lymphocyte recruitment. This response enhanced anti-viral innate immunity and reduced virus-induced airway inflammation.

The Pristionchus HOX gene Ppa-lin-39 inhibits programmed cell death to specify the vulva equivalence group and is not required during vulval induction

Development ◽  
1998 ◽  
Vol 125 (19) ◽  
pp. 3865-3873 ◽  
Author(s):  
R.J. Sommer ◽  
A. Eizinger ◽  
K.Z. Lee ◽  
B. Jungblut ◽  
A. Bubeck ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Nematode Species ◽  
Precursor Cells ◽  
Body Region ◽  
Ras Signaling ◽  
Equivalence Group ◽  
Hox Gene ◽  
C Elegans ◽  
Vulval Precursor Cells

In the two nematode species Caenorhabditis elegans and Pristionchus pacificus the vulva equivalence group in the central body region is specified by the Hox gene lin-39. C. elegans lin-39 mutants are vulvaless and the vulval precursor cells fuse with the surrounding hypodermis, whereas in P. pacificus lin-39 mutants the vulval precursor cells die by apoptosis. Mechanistically, LIN-39 might inhibit non-vulval fate (cell fusion in C. elegans, apoptosis in P. pacificus), promote vulval fate or do both. To study the mechanism of lin-39 function, we isolated P. pacificus cell death mutants and identified mutations in ced-3. Surprisingly, P. pacificus ced-3; lin-39 double mutants form a functional vulva in the absence of LIN-39 activity. Thus, in P. pacificus lin-39 specifies the vulva equivalence group by inhibiting programmed cell death. Furthermore, these data reveal an important difference in a later function of lin-39 between the two species. In C. elegans, LIN-39 specifies vulval cell fates in response to inductive RAS signaling, and in P. pacificus LIN-39 is not required for vulval induction. Thus, the comparative analysis indicates that lin-39 has distinct functions in both species although the gene is acting in a homologous developmental system.

scholarly journals An ankyrin-related gene (unc-44) is necessary for proper axonal guidance in Caenorhabditis elegans.

1995 ◽  
Vol 129 (4) ◽  
pp. 1081-1092 ◽  
Author(s):  
A J Otsuka ◽  
R Franco ◽  
B Yang ◽  
K H Shim ◽  
L Z Tang ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Nucleotide Sequence ◽  
Axon Guidance ◽  
Axonal Guidance ◽  
Related Gene ◽  
Sequence Analyses ◽  
Molecular Analyses ◽  
Molecular Studies ◽  
Alternatively Spliced ◽  
Related Proteins

Caenorhabditis elegans unc-44 mutations result in aberrant axon guidance and fasciculation with inappropriate partners. The unc-44 gene was cloned by transposon tagging, and verified by genetic and molecular analyses of six transposon-induced alleles and their revertants. Nucleotide sequence analyses demonstrated that unc-44 encodes a series of putative ankyrin-related proteins, including AO49 ankyrin (1815 aa, 198.8 kD), AO66 ankyrin (1867 aa, 204 kD), and AO13 ankyrin (&lt; or = 4700 aa, &lt; or = 517 kD). In addition to the major set of approximately 6 kb alternatively spliced transcripts, minor transcripts were observed at approximately 3, 5, 7, and 14 kb. Evidence is provided that mutations in the approximately 14-kb AO13 ankyrin transcript are responsible for the neuronal defects. These molecular studies provide the first evidence that ankyrin-related molecules are required for axonal guidance.

Comparative developmental studies using Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae)

Nematology ◽  
2000 ◽  
Vol 2 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Marie Delattre ◽  
Marie-Laure Dichtel ◽  
Marie-Anne Félix
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Analysis ◽  
Precursor Cells ◽  
Developmental Studies ◽  
Morphological Markers ◽  
Molecular Tools ◽  
Ras Gene ◽  
C Elegans ◽  
Vulval Precursor Cells ◽  
Anchor Cell

AbstractIn order to study the evolution of nematode vulva development, we focus on Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae) in comparison with Caenorhabditis elegans. In this species, the fates of the vulval precursor cells are determined by two successive nested inductions by the uterine anchor cell (instead of a single one in C. elegans). This hermaphroditic species can be cultured and handled like C. elegans. We review vulva development in this species. We present some molecular tools and the sequence of the Ras gene. This species is amenable to genetic analysis and we discuss the isolation of morphological markers. Afin d’étudier l’évolution du développement de la vulve des nématodes, nous nous concentrons sur l’espèce Oscheius/Dolichorhabditis sp. CEW1 (Rhabditidae) en la comparant à Caenorhabditis elegans. Dans cette espèce, les destinées des cellules précurseurs de la vulve sont déterminées par deux inductions emboîtées provenant de la cellule ancre de l’utérus (au lieu d’une seule chez C. elegans). Cette espèce hermaphrodite peut être élévée et manipulée comme C. elegans. Nous décrivons le développement de la vulve dans cette espèce. Nous présentons des outils moléculaires et la séquence du gène Ras. Les analyses génétiques sont possibles dans cette espèce et nous discutons l’isolement de marqueurs morphologiques.

Effects of corticosteroid-induced apoptosis on airway epithelial wound closure in vitro

2006 ◽  
Vol 291 (4) ◽  
pp. L794-L801 ◽  
Author(s):  
Delbert R. Dorscheid ◽  
Benjamin J. Patchell ◽  
Oscar Estrada ◽  
Bertha Marroquin ◽  
Roberta Tse ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Untreated Control ◽  
Wound Closure ◽  
Airway Epithelial Cell ◽  
Airway Epithelial ◽  
Wound Area ◽  
Epithelial Cell Migration

Damage to the airway epithelium is common in asthma. Corticosteroids induce apoptosis in and suppress proliferation of airway epithelial cells in culture. Whether apoptosis contributes to impaired epithelial cell repair after injury is not known. We examined whether corticosteroids would impair epithelial cell migration in an in vitro model of wound closure. Wounds (∼0.5–1.3 mm2) were created in cultured 1HAEo−human airway epithelial cell monolayers, after which cells were treated with up to 10 μM dexamethasone or budesonide for 24 h. Cultured cells were pretreated for 24 or 48 h with dexamethasone to observe the effect of long-term exposure on wound closure. After 12 h, the remaining wound area in monolayers pretreated for 48 h with 10 μM dexamethasone was 43 ± 18% vs. 10 ± 8% for untreated control monolayers. The addition of either corticosteroid immediately after injury did not slow closure significantly. After 12 h the remaining wound area in monolayers treated with 10 μM budesonide was 39 ± 4% vs. 43 ± 3% for untreated control monolayers. The proportion of apoptotic epithelial cells as measured by terminal deoxynucleotidyltransferase-mediated dUTP biotin nick end labeling both at and away from the wound edge was higher in monolayers treated with budesonide compared with controls. However, wound closure in the apoptosis-resistant 1HAEo−.Bcl-2+cell line was not different after dexamethasone treatment. We demonstrate that corticosteroid treatment before mechanical wounding impairs airway epithelial cell migration. The addition of corticosteroids after injury does not slow migration, despite their ability to induce apoptosis in these cells.

scholarly journals Inhibition of mucin secretion via glucocorticoid-induced regulation of calcium-related proteins in mouse lung

2018 ◽  
Vol 314 (6) ◽  
pp. L956-L966 ◽  
Author(s):  
Jin Yong An ◽  
Changhwan Ahn ◽  
Hee Young Kang ◽  
Eui-Bae Jeung
Keyword(s):  
Gene Expression ◽  
Transient Receptor Potential ◽  
Periodic Acid ◽  
Mucus Secretion ◽  
Mouse Lung ◽  
Alveolar Type ◽  
Related Gene ◽  
Mucin Secretion ◽  
Calbindin D ◽  
Related Proteins

Calcium is important for physiological functioning in many tissues and is essential in mucus secretion and muscle contraction. Intracellular concentrations of calcium are regulated by calcium-related proteins, such as transient receptor potential cation channel subfamily V member 4 (TRPV 4), TRPV6, Calbindin-D9k (CaBP-9k), sodium-calcium exchanger (NCX1), and plasma membrane Ca2+ ATPase 1 (PMCA1). In this study, the relationship between secretion of pulmonary mucus and calcium regulation was investigated. To confirm the effect of steroid hormones, immature mice were injected with estrogen (E2) or progesterone (P4), and mature mice were injected with dexamethasone (DEX). Subsequently, the location and expression of TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 in lung tissue were examined. Periodic acid-Schiff staining was performed to investigate functional aspects of the protein expression. There were no significant differences in calcium-related gene expression in E2- and P4-treated mice, but TRPV4, NCX1, and PMCA1 were increased in DEX-treated mice and were recovered by RU486 treatment. DEX induces the expression of calcium-related proteins through the glucocorticoid receptor-mediated pathway and may involve decreased mucin secretion in the bronchiole. TRPV4, TRPV6, CaBP-9k, NCX1, and PMCA1 were specifically expressed in Clara and alveolar type 2 cells of mouse lung. CC10, a marker of Clara cells, was decreased by DEX. In addition, mucin secretion, which is a functional aspect of this cell, was also decreased by DEX treatment. Control of calcium-related gene expression may affect the control of mucus secretion in the lung. Such a control mechanism can form the basis of studies into diseases such as inflammation attributable to mucus secretion abnormalities, coughing, and respiratory disorders and distress.

scholarly journals Activation of protein kinase A accelerates bovine bronchial epithelial cell migration

2002 ◽  
Vol 282 (5) ◽  
pp. L1108-L1116 ◽  
Author(s):  
John R. Spurzem ◽  
Jitendrakumar Gupta ◽  
Thomas Veys ◽  
Kristen R. Kneifl ◽  
Stephen I. Rennard ◽  
...  
Keyword(s):  
Cell Migration ◽  
Protein Kinase ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Protein Kinase A ◽  
Bronchial Epithelial Cell ◽  
Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Epithelial Cell Migration ◽  
Kinase A

Bronchial epithelial cell migration is required for the repair of damaged airway epithelium. We hypothesized that bronchial epithelial cell migration during wound repair is influenced by cAMP and the activity of its cyclic nucleotide-dependent protein kinase, protein kinase A (PKA). We found that, when confluent monolayers of bronchial epithelial cells are wounded, an increase in PKA activity occurs. Augmentation of PKA activity with a cell-permeable analog of cAMP, dibutyryl adenosine 3′,5′-cyclic monophosphate, isoproterenol, or a phosphodiesterase inhibitor accelerated migration of normal bronchial epithelial cells in in vitro wound closure assays and Boyden chamber migration assays. A role for PKA activity was also confirmed with a PKA inhibitor, KT-5720, which reduced stimulated migration. Augmentation of PKA activity reduced the levels of active Rho and the formation of focal adhesions. These studies suggest that PKA activation modulates Rho activity, migration mechanisms, and thus bronchial epithelial repair mechanisms.

Correct Hox gene expression established independently of position in Caenorhabditis elegans

Nature ◽  
1996 ◽  
Vol 382 (6589) ◽  
pp. 353-356 ◽  
Author(s):  
Deborah Cowing ◽  
Cynthia Kenyon
Keyword(s):  
Gene Expression ◽  
Caenorhabditis Elegans ◽  
Hox Gene
Sign in / Sign up

Export Citation Format

Share Document