scholarly journals Role of foxj1 and estrogen receptor alpha in ciliated epithelial cell differentiation of the neonatal oviduct

2004 ◽  
Vol 32 (3) ◽  
pp. 615-625 ◽  
Author(s):  
A Okada ◽  
Y Ohta ◽  
SL Brody ◽  
H Watanabe ◽  
A Krust ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Critical Role ◽  
Proliferating Cells ◽  
Epithelial Cell Differentiation ◽  
Ciliated Epithelial Cell ◽  
Ciliated Epithelial Cells ◽  
Deficient Mice

Estrogen regulates proliferation and differentiation of epithelial cells in the mammalian oviduct, but pathways for cell-specific differentiation are not well understood. In the epithelial cells of the developing rat oviduct, we found estrogen receptor (ER) alpha is expressed at birth and persists in all cells through neonatal day (ND) 7 when ciliated cells appear. To determine a specific function of ER and foxj1, a transcription factor known to have fundamental roles in ciliogenesis in the lung, in differentiation of the ciliated epithelial cells, we treated newborn rats from ND 0 to 5 with estradiol-17beta (E2) with and without a selective ER antagonist. E2 enhanced the number of proliferating cells and accelerated the process of epithelial cell differentiation resulting in ciliogenesis by ND 5, and co-treatment with an ER antagonist inhibited these changes. Foxj1 was expressed only in the infundibulum and ampulla (INF/AMP). That expression preceded the appearance of cilia and was induced by E2. Cilia were absent in oviducts of foxj1-deficient mice, indicating that foxj1 plays a critical role in oviductal ciliogenesis. However, we found the presence of cilia in the ERalpha-deficient mouse oviduct. The widespread expression of ERalpha in oviductal epithelium, but restriction of cilia to the INF/AMP regions, and importantly, the presence of cilia in the ERalpha-deficient mice, suggested ER signaling is not essential for ciliated epithelial cell differentiation. These observations demonstrate that, although E2 stimulates the differentiation process of ciliated epithelial cells, foxj1 is directly required for epithelial cell ciliogenesis of the neonatal oviduct.

scholarly journals Hypoxia Inducible Factor 3α Plays a Critical Role in Alveolarization and Distal Epithelial Cell Differentiation during Mouse Lung Development

PLoS ONE ◽  
2013 ◽  
Vol 8 (2) ◽  
pp. e57695 ◽  
Author(s):  
Yadi Huang ◽  
Joshua Kapere Ochieng ◽  
Marjon Buscop-van Kempen ◽  
Anne Boerema-de Munck ◽  
Sigrid Swagemakers ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Lung Development ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Mouse Lung ◽  
Epithelial Cell Differentiation

scholarly journals Cell cycle-targeting microRNAs promote differentiation by enforcing cell-cycle exit

2017 ◽  
Vol 114 (40) ◽  
pp. 10660-10665 ◽  
Author(s):  
Tobias Otto ◽  
Sheyla V. Candido ◽  
Mary S. Pilarz ◽  
Ewa Sicinska ◽  
Roderick T. Bronson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Airway Disease ◽  
Quiescent State ◽  
Cell Cycle Exit ◽  
Epithelial Cell Differentiation ◽  
Chronic Airway Disease

MicroRNAs (miRNAs) have been known to affect various biological processes by repressing expression of specific genes. Here we describe an essential function of the miR-34/449 family during differentiation of epithelial cells. We found that miR-34/449 suppresses the cell-cycle machinery in vivo and promotes cell-cycle exit, thereby allowing epithelial cell differentiation. Constitutive ablation of all six members of this miRNA family causes derepression of multiple cell cycle-promoting proteins, thereby preventing epithelial cells from exiting the cell cycle and entering a quiescent state. As a result, formation of motile multicilia is strongly inhibited in several tissues such as the respiratory epithelium and the fallopian tube. Consequently, mice lacking miR-34/449 display infertility as well as severe chronic airway disease leading to postnatal death. These results demonstrate that miRNA-mediated repression of the cell cycle is required to allow epithelial cell differentiation.

Estrogen Receptor-Beta Regulates Epithelial Cell Differentiation in the Mouse Ventral Prostate

2004 ◽  
Vol 62 (3) ◽  
pp. 115-115 ◽  
Author(s):  
Otabek Imamov ◽  
Andrea Morani ◽  
Gil Jin Shim ◽  
Yoko Omoto ◽  
Margaret Warner ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Estrogen Receptor Beta ◽  
Ventral Prostate ◽  
Epithelial Cell Differentiation ◽  
Receptor Beta

scholarly journals Differentiation-Dependent LMP1 Expression Is Required for Efficient Lytic Epstein-Barr Virus Reactivation in Epithelial Cells

2017 ◽  
Vol 91 (8) ◽  
Author(s):  
Dhananjay M. Nawandar ◽  
Makoto Ohashi ◽  
Reza Djavadian ◽  
Elizabeth Barlow ◽  
Kathleen Makielski ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Lytic Infection ◽  
Barr Virus ◽  
Epithelial Cell Differentiation ◽  
Hairy Leukoplakia ◽  
Lmp1 Expression ◽  
Lytic Reactivation ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV)-associated diseases of epithelial cells, including tumors that have latent infection, such as nasopharyngeal carcinoma (NPC), and oral hairy leukoplakia (OHL) lesions that have lytic infection, frequently express the viral latent membrane protein 1 (LMP1). In lytically infected cells, LMP1 expression is activated by the BRLF1 (R) immediate early (IE) protein. However, the mechanisms by which LMP1 expression is normally regulated in epithelial cells remain poorly understood, and its potential roles in regulating lytic reactivation in epithelial cells are as yet unexplored. We previously showed that the differentiation-dependent cellular transcription factors KLF4 and BLIMP1 induce lytic EBV reactivation in epithelial cells by synergistically activating the two EBV immediate early promoters (Zp and Rp). Here we show that epithelial cell differentiation also induces LMP1 expression. We demonstrate that KLF4 and BLIMP1 cooperatively induce the expression of LMP1, even in the absence of the EBV IE proteins BZLF1 (Z) and R, via activation of the two LMP1 promoters. Furthermore, we found that differentiation of NOKs-Akata cells by either methylcellulose suspension or organotypic culture induces LMP1 expression prior to Z and R expression. We show that LMP1 enhances the lytic infection-inducing effects of epithelial cell differentiation, as well as 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate treatment, in EBV-infected epithelial cells by increasing expression of the Z and R proteins. Our results suggest that differentiation of epithelial cells activates a feed-forward loop in which KLF4 and BLIMP1 first activate LMP1 expression and then cooperate with LMP1 to activate Z and R expression. IMPORTANCE The EBV protein LMP1 is expressed in EBV-associated epithelial cell diseases, regardless of whether these diseases are due to lytic infection (such as oral hairy leukoplakia) or latent infection (such as nasopharyngeal carcinoma). However, surprisingly little is known about how LMP1 expression is regulated in epithelial cells, and there are conflicting reports about whether it plays any role in regulating viral lytic reactivation. In this study, we show that epithelial cell differentiation induces LMP1 expression by increasing expression of two cellular transcription factors (KLF4 and BLIMP1) which cooperatively activate the two LMP1 promoters. We also demonstrate that LMP1 promotes efficient lytic reactivation in EBV-infected epithelial cells by enhancing expression of the Z and R proteins. Thus, in EBV-infected epithelial cells, LMP1 expression is promoted by differentiation and positively regulates lytic viral reactivation.

scholarly journals Pretreatment of aged mice with retinoic acid restores alveolar regeneration via upregulation of reciprocal PDGFRA signaling

2020 ◽  
Author(s):  
Jason J. Gokey ◽  
John Snowball ◽  
Jenna Green ◽  
Marion Waltamath ◽  
Jillian J. Spinney ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cell ◽  
Aged Mice ◽  
Alveolar Epithelial ◽  
Epithelial Cell Differentiation ◽  
Lung Repair

AbstractObjectivesIdiopathic Pulmonary Fibrosis (IPF) primarily affects the aged population and is characterized by failure of alveolar regeneration leading to loss of alveolar type 1 cells (AT1). Aged mouse models of lung repair have demonstrated that regeneration fails with increased age. Mouse and rat lung repair models have shown retinoic acid (RA) treatment can restore alveolar regeneration. Herein we seek to determine the signaling mechanisms by which RA treatment prior to injury supports alveolar differentiation.DesignPartial pneumonectomy (PNX) lung injury model and next generation sequencing of sorted cell populations are used to uncover molecular targets regulating alveolar repair. In-vitro organoids generated from Mouse or IPF patient epithelial cells co-cultured with young, aged, or RA pretreated murine mesenchyme are used to test potential targets.Main outcome measurementsKnown alveolar epithelial cell differentiation markers, including HOPX and AGER for AT1 cells are used to assess outcome of treatments.ResultsGene expression analysis of sorted fibroblasts and epithelial cells isolated from lungs of young, aged, and RA treated aged mice predicted increased PDGFA signaling that coincided with regeneration and alveolar epithelial differentiation. Addition of PDGFA induced AT1 and AT2 alveolar differentiation in both mouse and human IPF lung organoids generated with aged fibroblasts and PDGFA monoclonal antibody blocked AT1 cell differentiation in organoids generated with young murine fibroblasts.ConclusionsOur data support the concept that reciprocal PDGFA signaling activates regenerative fibroblasts that support alveolar epithelial cell differentiation and repair, providing a potential therapeutic strategy to influence the pathogenesis of IPF.Key QuestionWhich epithelial-mesenchymal crosstalk pathways are activated by RA pretreatment of aged lungs that support realveolarization after partial pneumonectomy surgery?Bottom LineIncreased PDGFA/PDGFRA signaling in aged lungs promotes regenerative activation of interstitial matrixfibroblast which is required for AT2 to AT1 differentiation and alveolar regeneration.Read OnIn-vitro and in-vivo analysis demonstrated that PDGFA signaling supports alveolar matrixfibroblast and AT1 epithelial cell differentiation, both necessary for alveolar regeneration in aged lungs.

scholarly journals Measles Virus Infection Induces Terminal Differentiation of Human Thymic Epithelial Cells

1999 ◽  
Vol 73 (3) ◽  
pp. 2212-2221 ◽  
Author(s):  
Hélène Valentin ◽  
Olga Azocar ◽  
Branka Horvat ◽  
Rejane Williems ◽  
Robert Garrone ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Virus Infection ◽  
Measles Virus ◽  
Terminal Differentiation ◽  
Thymic Epithelial Cells ◽  
Thymic Epithelial Cell ◽  
Epithelial Cell Line ◽  
Epithelial Cell Differentiation

ABSTRACT Measles virus infection induces a profound immunosuppression that may lead to serious secondary infections and mortality. In this report, we show that the human cortical thymic epithelial cell line is highly susceptible to measles virus infection in vitro, resulting in infectious viral particle production and syncytium formation. Measles virus inhibits thymic epithelial cell growth and induces an arrest in the G0/G1 phases of the cell cycle. Moreover, we show that measles virus induces a progressive thymic epithelial cell differentiation process: attached measles virus-infected epithelial cells correspond to an intermediate state of differentiation while floating cells, recovered from cell culture supernatants, are fully differentiated. Measles virus-induced thymic epithelial cell differentiation is characterized by morphological and phenotypic changes. Measles virus-infected attached cells present fusiform and stellate shapes followed by a loss of cell-cell contacts and a shift from low- to high-molecular-weight keratin expression. Measles virus infection induces thymic epithelial cell apoptosis in terminally differentiated cells, revealed by the condensation and degradation of DNA in measles virus-infected floating thymic epithelial cells. Because thymic epithelial cells are required for the generation of immunocompetent T lymphocytes, our results suggest that measles virus-induced terminal differentiation of thymic epithelial cells may contribute to immunosuppression, particularly in children, in whom the thymic microenvironment is of critical importance for the development and maturation of a functional immune system.

Mammary epithelial cell differentiation in vitro is regulated by an interplay of EGF action and tenascin-C downregulation

1995 ◽  
Vol 108 (6) ◽  
pp. 2445-2456 ◽  
Author(s):  
G. Wirl ◽  
M. Hermann ◽  
P. Ekblom ◽  
R. Fassler
Keyword(s):  
Mammary Gland ◽  
Cell Differentiation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Mammary Epithelial Cell ◽  
Mammary Epithelial ◽  
Potent Inducer ◽  
Tenascin C ◽  
Epithelial Cell Differentiation

Expression of the extracellular matrix glycoprotein tenascin-C in the mammary gland is associated with cellular proliferation and cell motility during organogenesis and tumorigenesis. Because the source and the regulation of tenascin-C in these tissues are unclear, we have used tenascin-C cDNA, FITC-immunofluorescence and immuno-precipitation to examine tenascin-C expression of mammary epithelial cells. Using several mammary epithelial cell lines we could show that tenascin-C can be produced and secreted by epithelial cells. However it was found that tenascin-C synthesis was inversely correlated with the polarized epithelial phenotype. Among three mouse mammary epithelial cell clones, tenascin-C expression was most abundant in HC-11 cells, the least differentiated cell type. Expression levels were high during the growth phase but were nearly abolished when cells were grown to confluence and induced to express milk proteins. Downregulation of tenascin-C by EGF apparently commits HC-11 cells to respond to lactogenic hormones and consequently, hormone induced levels of beta-casein mRNA decreased significantly when HC-11 cells were grown on a tenascin-C substrate. On the other hand, TGF-beta, another growth factor involved in coordinated growth and differentiation of the mammary gland in vivo was found to be a very potent inducer of tenascin-C. The generation of fully polarized and tight epithelium affected the levels of tenascin-C expression. In contrast to HC-11 cells, which do not form epithelial domes in vitro, highly polarized and dome forming EpH4 and Fos-ER cells nearly lacked tenascin-C. Similarly, induction of dome formation in the rat mammary stem cell line Rama 25 by the differentiation inducer dimethylsulfoxide caused a loss of TN-C-transcripts. The inability of Fos-ER cells to develop domes in the presence of soluble tenascin-C also suggests its interference with induction and maintenance of mammary epithelial cell differentiation.

Increased lung expansion alters lung growth but not alveolar epithelial cell differentiation in newborn lambs

2007 ◽  
Vol 292 (2) ◽  
pp. L454-L461 ◽  
Author(s):  
S. J. Flecknoe ◽  
K. J. Crossley ◽  
G. M. Zuccala ◽  
J. E. Searle ◽  
B. J. Allison ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Epithelial Cell ◽  
Alveolar Epithelial Cell ◽  
Surfactant Protein ◽  
Mrna Levels ◽  
Lung Growth ◽  
Proliferating Cells ◽  
Alveolar Epithelial ◽  
Epithelial Cell Differentiation ◽  
Lung Expansion

Although increased lung expansion markedly alters lung growth and epithelial cell differentiation during fetal life, the effect of increasing lung expansion after birth is unknown. We hypothesized that increased basal lung expansion, caused by ventilating newborn lambs with a positive end-expiratory pressure (PEEP), would stimulate lung growth and alter alveolar epithelial cell (AEC) proportions and decrease surfactant protein mRNA levels. Two groups of lambs were sedated and ventilated with either 0 cmH2O PEEP (controls, n = 5) or 10 cmH2O PEEP ( n = 5) for 48 h beginning at 15 ± 1 days after normal term birth. A further group of nonventilated 2-wk-old lambs was used for comparison. We determined wet and dry lung weights, DNA and protein content, a labeling index for proliferating cells, surfactant protein mRNA expression, and proportions of AECs using electron microscopy. Although ventilating lambs for 48 h with 10 cmH2O PEEP did not affect total lung DNA or protein, it significantly increased the proportion of proliferating cells in the lung when compared with nonventilated 2-wk-old controls and lambs ventilated with 0 cmH2O PEEP (control: 2.6 ± 0.5%; 0 PEEP: 1.9 ± 0.3%; 10 PEEP: 3.5 ± 0.3%). In contrast, no differences were observed in AEC proportions or surfactant protein mRNA levels between either of the ventilated groups. This study demonstrates that increases in end-expiratory lung volumes, induced by the application of PEEP, lead to increased lung growth in mechanically ventilated 2-wk-old lambs but do not alter the proportions of AECs.

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