scholarly journals P7‐24: Up‐regulation of LIM/homeobox protein LHX9 in alveolar epithelial type 2 cells of COPD lungs

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 267-267
Keyword(s):  
Alveolar Epithelial ◽  
Homeobox Protein

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.

Retinoic acid-induced proliferation of lung alveolar epithelial cells: relation with the IGF system

1998 ◽  
Vol 275 (1) ◽  
pp. L71-L79 ◽  
Author(s):  
Elodie Nabeyrat ◽  
Valérie Besnard ◽  
Sophie Corroyer ◽  
Véronique Cazals ◽  
Annick Clement
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Growth Factor ◽  
Alveolar Epithelium ◽  
Cell Number ◽  
Dependent Manner ◽  
Alveolar Epithelial ◽  
Igf System ◽  
Tgf Β1

Retinoids, including retinol and retinoic acid (RA) derivatives, are important molecules for lung growth and homeostasis. The presence of RA receptors and of RA-binding proteins in the alveolar epithelium led to suggest a role for RA on alveolar epithelial cell replication. In the present study, we examined the effects of RA on proliferation of the stem cells of the alveolar epithelium, the type 2 cells. We showed that treatment of serum-deprived type 2 cells with RA led to a stimulation of cell proliferation, with an increase in cell number in a dose-dependent manner. To gain some insights into the mechanisms involved, we studied the effects of RA on the expression of several components of the insulin-like growth factor (IGF) system that have been shown to be associated with the growth arrest of type 2 cells, mainly the IGF-binding protein-2 (IGFBP-2), IGF-II, and the type 2 IGF receptor. We documented a marked decrease in the expression of these components upon RA treatment. Using conditioned media from RA-treated cells, we provided evidence that the proliferative response of type 2 cells to RA was mediated through production of growth factor(s) distinct from IGF-I. We also showed that RA was able to reduce the decrease in cell number observed when type 2 cells were treated with transforming growth factor (TGF)-β1. These results together with the known stimulatory effect of TGF-β1 on IGFBP-2 expression led to suggest that RA may be associated with type 2 cell proliferation through mechanisms interfering with the TGF-β1 pathway.

scholarly journals Adipose Tissue-Derived Stem Cells Have the Ability to Differentiate into Alveolar Epithelial Cells and Ameliorate Lung Injury Caused by Elastase-Induced Emphysema in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Eriko Fukui ◽  
Soichiro Funaki ◽  
Kenji Kimura ◽  
Toru Momozane ◽  
Atsuomi Kimura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Alveolar Cells ◽  
Alveolar Epithelial

Chronic obstructive pulmonary disease is a leading cause of mortality globally, with no effective therapy yet established. Adipose tissue-derived stem cells (ADSCs) are useful for ameliorating lung injury in animal models. However, whether ADSCs differentiate into functional cells remains uncertain, and no study has reported on the mechanism by which ADSCs improve lung functionality. Thus, in this study, we examined whether ADSCs differentiate into lung alveolar cells and are able to ameliorate lung injury caused by elastase-induced emphysema in model mice. Here, we induced ADSCs to differentiate into type 2 alveolar epithelial cells in vitro. We demonstrated that ADSCs can differentiate into type 2 alveolar epithelial cells in an elastase-induced emphysematous lung and that ADSCs improve pulmonary function of emphysema model mice, as determined with spirometry and 129Xe MRI. These data revealed a novel function for ADSCs in promoting repair of the damaged lung by direct differentiation into alveolar epithelial cells.

Apoptosis and DNA damage in type 2 alveolar epithelial cells cultured from hyperoxic rats

1998 ◽  
Vol 274 (5) ◽  
pp. L714-L720 ◽  
Author(s):  
Sue Buckley ◽  
Lora Barsky ◽  
Barbara Driscoll ◽  
Kenneth Weinberg ◽  
Kathryn D. Anderson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Epithelial Cells ◽  
Cellular Response ◽  
Ex Vivo ◽  
Keratinocyte Growth Factor ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Dna Laddering

Apoptosis is a genetically controlled cellular response to developmental stimuli and environmental insult that culminates in cell death. Sublethal hyperoxic injury in rodents is characterized by a complex but reproducible pattern of lung injury and repair during which the alveolar surface is damaged, denuded, and finally repopulated by type 2 alveolar epithelial cells (AEC2). Postulating that apoptosis might occur in AEC2 after hyperoxic injury, we looked for the hallmarks of apoptosis in AEC2 from hyperoxic rats. A pattern of increased DNA end labeling, DNA laddering, and induction of p53, p21, and Bax proteins, strongly suggestive of apoptosis, was seen in AEC2 cultured from hyperoxic rats when compared with control AEC2. In contrast, significant apoptosis was not detected in freshly isolated AEC2 from oxygen-treated rats. Thus the basal culture conditions appeared to be insufficient to ensure the ex vivo survival of AEC2 damaged in vivo. The oxygen-induced DNA strand breaks were blocked by the addition of 20 ng/ml of keratinocyte growth factor (KGF) to the culture medium from the time of plating and were partly inhibited by Matrigel or a soluble extract of Matrigel. KGF treatment resulted in a partial reduction in the expression of the p21, p53, and Bax proteins but had no effect on DNA laddering. We conclude that sublethal doses of oxygen in vivo cause damage to AEC2, resulting in apoptosis in ex vivo culture, and that KGF can reduce the oxygen-induced DNA damage. We speculate that KGF plays a role as a survival factor in AEC2 by limiting apoptosis in the lung after acute hyperoxic injury.

scholarly journals ResolvinD1 reduces apoptosis and inflammation in primary human alveolar epithelial type 2 cells

2016 ◽  
Vol 96 (5) ◽  
pp. 526-536 ◽  
Author(s):  
Wanli Xie ◽  
Huiqing Wang ◽  
Qing Liu ◽  
Yongsheng Li ◽  
Jianjun Wang ◽  
...  
Keyword(s):  
Alveolar Epithelial ◽  
Apoptosis And Inflammation
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