scholarly journals Differential Regulation of Gene Expression of Alveolar Epithelial Cell Markers in Human Lung Adenocarcinoma-Derived A549 Clones

2015 ◽  
Vol 2015 ◽  
pp. 1-20 ◽  
Author(s):  
Hiroshi Kondo ◽  
Keiko Miyoshi ◽  
Shoji Sakiyama ◽  
Akira Tangoku ◽  
Takafumi Noma
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Mapk Pathway ◽  
Alveolar Epithelial Cell ◽  
Marker Gene ◽  
Regulation Of Gene Expression ◽  
Surfactant Protein ◽  
Specific Gene ◽  
Expression Levels ◽  
Alveolar Epithelial

Stem cell therapy appears to be promising for restoring damaged or irreparable lung tissue. However, establishing a simple and reproducible protocol for preparing lung progenitor populations is difficult because the molecular basis for alveolar epithelial cell differentiation is not fully understood. We investigated anin vitrosystem to analyze the regulatory mechanisms of alveolus-specific gene expression using a human alveolar epithelial type II (ATII) cell line, A549. After cloning A549 subpopulations, each clone was classified into five groups according to cell morphology and marker gene expression. Two clones (B7 and H12) were further analyzed. Under serum-free culture conditions,surfactant protein C(SPC), an ATII marker, was upregulated in both H12 and B7.Aquaporin 5(AQP5), an ATI marker, was upregulated in H12 and significantly induced in B7. When the RAS/MAPK pathway was inhibited,SPCandthyroid transcription factor-1(TTF-1) expression levels were enhanced. After treatment with dexamethasone (DEX), 8-bromoadenosine 3′5′-cyclic monophosphate (8-Br-cAMP), 3-isobutyl-1-methylxanthine (IBMX), and keratinocyte growth factor (KGF),surfactant protein BandTTF-1expression levels were enhanced. We found that A549-derived clones have plasticity in gene expression of alveolar epithelial differentiation markers and could be useful in studying ATII maintenance and differentiation.

GATA6 regulates differentiation of distal lung epithelium

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2233-2246 ◽  
Author(s):  
Honghua Yang ◽  
Min Min Lu ◽  
Lili Zhang ◽  
Jeffrey A. Whitsett ◽  
Edward E. Morrisey
Keyword(s):  
Gene Expression ◽  
Epithelial Cell ◽  
Surfactant Protein ◽  
Gata Factor ◽  
Lung Epithelium ◽  
Alveolar Epithelial ◽  
Distal Lung ◽  
Transgenic Embryos

GATA6 is a member of the GATA family of zinc-finger transcriptional regulators and is the only known GATA factor expressed in the distal epithelium of the lung during development. To define the role that GATA6 plays during lung epithelial cell development, we expressed a GATA6-Engrailed dominant-negative fusion protein in the distal lung epithelium of transgenic mice. Transgenic embryos lacked detectable alveolar epithelial type 1 cells in the distal airway epithelium. These embryos also exhibited increased Foxp2 gene expression, suggesting a disruption in late alveolar epithelial differentiation. Alveolar epithelial type 2 cells, which are progenitors of alveolar epithelial type 1 cells, were correctly specified as shown by normal thyroid transcription factor 1 and surfactant protein A gene expression. However, attenuated endogenous surfactant protein C expression indicated that alveolar epithelial type 2 cell differentiation was perturbed in transgenic embryos. The number of proximal airway tubules is also reduced in these embryos, suggesting a role for GATA6 in regulating distal-proximal airway development. Finally, a functional role for GATA factor function in alveolar epithelial type 1 cell gene regulation is supported by the ability of GATA6 to trans-activate the mouse aquaporin-5 promoter. Together, these data implicate GATA6 as an important regulator of distal epithelial cell differentiation and proximal airway development in the mouse.

scholarly journals Novel insights into surfactant protein C trafficking revealed through the study of a pathogenic mutant

2021 ◽  
pp. 2100267
Author(s):  
Jennifer A. Dickens ◽  
Eimear N. Rutherford ◽  
Susana Abreu ◽  
Joseph E. Chambers ◽  
Matthew O. Ellis ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Cell Surface ◽  
Protein C ◽  
Alveolar Epithelial Cell ◽  
Surfactant Protein ◽  
Surfactant Protein C ◽  
Alveolar Epithelial ◽  
Health And Disease

Alveolar epithelial cell dysfunction plays an important role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) but remains incompletely understood. Some monogenic forms of pulmonary fibrosis are associated with expression of mutant surfactant protein C (SFTPC). The commonest pathogenic mutant, I73T, mislocalises to the alveolar epithelial cell plasma membrane and displays a toxic-gain-of-function. Because the mechanisms explaining the link between this mutant and IPF are incompletely understood, we sought to interrogate SFTPC trafficking in health and disease to understand the functional significance of SFTPC-I73T relocalisation.We performed mechanistic analysis of SFTPC trafficking in a cell model that reproduces the in vivo phenotype and validated findings in human primary alveolar organoids.We show that wild-type SFTPC takes an unexpected indirect trafficking route via the plasma membrane and undergoes the first of multiple cleavage events before reaching the multivesicular body (MVB) for further processing. SFTPC-I73T takes this same route, but its progress is retarded both at the cell surface and due to failure of trafficking into the MVB. Unable to undergo onward trafficking, it is recycled to the plasma membrane as a partially cleaved intermediate.These data show for the first time that all SFTPC transits the cell surface during normal trafficking, and the I73T mutation accumulates at the cell surface through both retarded trafficking and active recycling. This understanding of normal SFTPC trafficking and how the I73T mutant disturbs it provides novel insight into SFTPC biology in health and disease, and in the contribution of the SFTPC mutant to IPF development.

Protective effect of IL-6 on alveolar epithelial cell death induced by hydrogen peroxide

2005 ◽  
Vol 288 (2) ◽  
pp. L342-L349 ◽  
Author(s):  
Hiroshi Kida ◽  
Mitsuhiro Yoshida ◽  
Shigenori Hoshino ◽  
Koji Inoue ◽  
Yukihiro Yano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Lung Fibroblasts ◽  
Alveolar Epithelial ◽  
Epithelial Cell Death

The goal of this study was to examine whether IL-6 could directly protect lung resident cells, especially alveolar epithelial cells, from reactive oxygen species (ROS)-induced cell death. ROS induced IL-6 gene expression in organotypic lung slices of wild-type (WT) mice. ROS also induced IL-6 gene expression in mouse primary lung fibroblasts, dose dependently. The organotypic lung slices of WT were more resistant to ROS-induced DNA fragmentation than those of IL-6-deficient (IL-6−/−) mice. WT resistance against ROS was abrogated by treatment with anti-IL-6 antibody. TdT-mediated dUTP nick end labeling stain and electron microscopy revealed that DNA fragmented cells in the IL-6−/− slice included alveolar epithelial cells and endothelial cells. In vitro studies demonstrated that IL-6 reduced ROS-induced A549 alveolar epithelial cell death. Together, these data suggest that IL-6 played an antioxidant role in the lung by protecting lung resident cells, especially alveolar epithelial cells, from ROS-induced cell death.

Changes in alveolar epithelial cell proportions during fetal and postnatal development in sheep

2003 ◽  
Vol 285 (3) ◽  
pp. L664-L670 ◽  
Author(s):  
S. J. Flecknoe ◽  
M. J. Wallace ◽  
M. L. Cock ◽  
R. Harding ◽  
S. B. Hooper
Keyword(s):  
Epithelial Cell ◽  
Important Determinant ◽  
Alveolar Epithelial Cell ◽  
Surfactant Protein ◽  
Type I ◽  
Mrna Levels ◽  
Type Ii ◽  
Alveolar Epithelial ◽  
Lung Expansion ◽  
Birth Type

Basal lung expansion is an important determinant of alveolar epithelial cell (AEC) phenotype in the fetus. Because basal lung expansion increases toward term and is reduced after birth, we hypothesized that these changes would be associated with altered proportions of AECs. AEC proportions were calculated with electron microscopy in fetal and postnatal sheep. Type I AECs increased from 4.8 ± 1.3% at 91 days to 63.0 ± 3.6% at 111 days of gestation, remained at this level until term, and decreased to 44.8 ± 1.8% after birth. Type II AECs increased from 4.3 ± 1.5% at 111 days to 29.6 ± 4.1% at 128 days of gestation, remained at this level until term, and then increased to 52.9 ± 1.5% after birth. Surfactant protein (SP)-A, -B and -C mRNA levels increased with increasing gestational age before birth, but the changes in SP expression after birth were inconsistent. Thus before birth type I AECs predominate, whereas after birth type II AECs predominate, possibly due to the reduction in basal lung expansion associated with the entry of air into the lungs.

scholarly journals Histone acetyltransferase MOZ acts as a co-activator of Nrf2–MafK and induces tumour marker gene expression during hepatocarcinogenesis

2007 ◽  
Vol 402 (3) ◽  
pp. 559-566 ◽  
Author(s):  
Kumiko Ohta ◽  
Megumi Ohigashi ◽  
Ayako Naganawa ◽  
Hiromi Ikeda ◽  
Masaharu Sakai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zinc Finger Protein ◽  
Binding Protein ◽  
Marker Gene ◽  
Regulation Of Gene Expression ◽  
Gene Activation ◽  
Tumour Marker ◽  
Specific Gene ◽  
Related Factor ◽  
Enhancer Element

HATs (histone acetyltransferases) contribute to the regulation of gene expression, and loss or dysregulation of these activities may link to tumorigenesis. Here, we demonstrate that expression levels of HATs, p300 and CBP [CREB (cAMP-response-element-binding protein)-binding protein] were decreased during chemical hepatocarcinogenesis, whereas expression of MOZ (monocytic leukaemia zinc-finger protein; MYST3) – a member of the MYST [MOZ, Ybf2/Sas3, Sas2 and TIP60 (Tat-interacting protein, 60 kDa)] acetyltransferase family – was induced. Although the MOZ gene frequently is rearranged in leukaemia, we were unable to detect MOZ rearrangement in livers with hyperplastic nodules. We examined the effect of MOZ on hepatocarcinogenic-specific gene expression. GSTP (glutathione S-transferase placental form) is a Phase II detoxification enzyme and a well-known tumour marker that is specifically elevated during hepatocarcinogenesis. GSTP gene activation is regulated mainly by the GPE1 (GSTP enhancer 1) enhancer element, which is recognized by the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2)–MafK heterodimer. We found that MOZ enhances GSTP promoter activity through GPE1 and acts as a co-activator of the Nrf2–MafK heterodimer. Further, exogenous MOZ induced GSTP expression in rat hepatoma H4IIE cells. These results suggest that during early hepatocarcinogenesis, aberrantly expressed MOZ may induce GSTP expression through the Nrf2-mediated pathway.

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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