scholarly journals Decreased expression of Met during differentiation in rat lung

2016 ◽  
Vol 60 (1) ◽  
Author(s):  
T. Kato ◽  
K. Oka ◽  
T. Nakamura ◽  
A. Ito
Keyword(s):  
Stem Cells ◽  
3D Culture ◽  
Immunofluorescence Assay ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Cell Marker ◽  
Epithelial Stem Cells ◽  
Club Cell ◽  
Adult Mice ◽  
Lung Epithelial

<p>Organ-specific stem cells play key roles in maintaining the epithelial cell layers of lung. Bronchioalveolar stem cells (BASCs) are distal lung epithelial stem cells of adult mice. Alveolar type 2 (AT2) cells have important functions and serve as progenitor cells of alveolar type 1 (AT1) cells to repair the epithelium when they are injured. Hepatocyte growth factor (HGF) elicits mitogenic, morphogenic, and anti-apoptotic effects on lung epithelial cells through tyrosine phosphorylation of Met receptor, and thus is recognized as a pulmotrophic factor. To understand which cells HGF targets in lung, we identified the cells expressing Met by immunofluorescence assay. Met was strongly expressed in BASCs, which expressed an AT2 cell marker, pro-SP-C, and a club cell marker, CCSP. In alveoli, we found higher expression of Met in primary AT2 than in AT1 cells, which was confirmed using primary AT2 cells. We further examined the mitogenic activity of HGF in AT2-cell-derived alveolar-like cysts (ALCs) in 3D culture. Multicellular ALCs expressed Met, and HGF enhanced the ALC production. Taking these findings together, BASCs could also be an important target for HGF, and HGF-Met signaling could function more potent on cells that have greater multipotency in adult lung.</p>

scholarly journals Regulation of alveolar type 2 stem/progenitor cells in lung injury and regeneration

2020 ◽  
Vol 52 (7) ◽  
pp. 716-722 ◽  
Author(s):  
Ailing Wu ◽  
Hai Song
Keyword(s):  
Stem Cells ◽  
Lung Injury ◽  
Progenitor Cells ◽  
Alveolar Epithelium ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Epithelial Stem Cells ◽  
Lung Structure ◽  
And Function

Abstract The renewal of lung epithelial cells is normally slow unless the lung is injured. The resident epithelial stem cells rapidly proliferate and differentiate to maintain lung structure and function when the lung is damaged. The alveolar epithelium is characterized by alveolar type 1 (AT1) and alveolar type 2 (AT2) cells. AT2 cells are the stem cells for alveoli, as they can both self-renew and generate AT1 cells. Abnormal proliferation and regulation of AT2 cells will lead to serious lung diseases including cancers. In this review, we focused on the alveolar stem/progenitor cells, the key physiological function of AT2 cells in lung homeostasis and the complicated regulation of AT2 cells in the repairing processes after lung injury.

scholarly journals Expression and Role of Oct3/4 in Injury-Repair Process of Rat Alveolar Epithelium after 5-Fu Treatment

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Wen-ya Li ◽  
Xu-lv Ye ◽  
Xin-shan Jia ◽  
Lan-ling Jia
Keyword(s):  
Stem Cells ◽  
Embryonic Stem ◽  
Alveolar Epithelium ◽  
Repair Process ◽  
Lung Epithelial Cells ◽  
Clara Cell ◽  
Epithelial Stem Cells ◽  
Injury Repair ◽  
Alveolar Epithelial ◽  
Lung Epithelial

Objective. We aimed to investigate how the embryonic stem cell-related gene Oct3/4 changes during the injury-repair process of distal pulmonary epithelium induced by 5-fluorouracil (5-Fu).Methods. We have developed the lung injury model induced by 5-Fu and observed the dynamic changes of Oct3/4 by indirect immunofluorescence, Western blot, and quantitative real-time PCR. Immunofluorescence double staining was used to compare the positions of Oct3/4(+) cells and other reported alveolar epithelial stem cells.Results. Oct3/4(+) cells were not found in normal rat lung epithelial cells. However, after treatment with 5-Fu, Oct3/4(+) cells appeared at 12 h, reached the peak at 24 h, then decreased at 48 h, and eventually disappeared at 72 h. Oct3/4 was localized in the nucleus. We found that the sites of Clara cell secretory protein and surfactant protein-C dual positive cells were apparently different from Oct3/4(+) cells.Conclusions. Our results revealed that, in rat alveolar epithelium, expression of Oct3/4 could be induced after treatment with 5-Fu, then decreased gradually, and was silenced following the alveolar epithelial differentiation. We hold that Oct3/4(+) cells are lung stem cells, which can provide new evidence for identification and isolation of lung epithelial stem cells.

Carbon nanoparticle-induced lung epithelial cell proliferation is mediated by receptor-dependent Akt activation

2008 ◽  
Vol 294 (2) ◽  
pp. L358-L367 ◽  
Author(s):  
Klaus Unfried ◽  
Ulrich Sydlik ◽  
Katrin Bierhals ◽  
Alexander Weissenberg ◽  
Josef Abel
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cells ◽  
Carbon Nanoparticles ◽  
Growth Factor Receptor ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Specific Cell ◽  
Akt Inhibitor ◽  
Signaling Mechanism ◽  
Lung Epithelial

Treatment of lung epithelial cells with different kinds of nano-sized particles leads to cell proliferation. Because bigger particles fail to induce this reaction, it is suggested that the special surface properties, due to the extremely small size of these kinds of materials, is the common principle responsible for this specific cell reaction. Here the activation of the protein kinase B (Akt) signaling cascade by carbon nanoparticles was investigated with regard to its relevance for proliferation. Kinetics and dose-response experiments demonstrated that Akt is specifically activated by nanoparticulate carbon particles in rat alveolar type II epithelial cells as well as in human bronchial epithelial cells. This pathway appeared to be dependent on epidermal growth factor receptor and β1-integrins. The activation of Akt by these receptors is known to be a feature of adhesion-dependent signaling. However, intracellular proteins described in this context (focal adhesion kinase pp125FAK and integrin-linked kinase) were not activated, indicating a specific signaling mechanism. Inhibitor studies demonstrate that nanoparticle-induced proliferation is mediated by phosphoinositide 3-kinases and Akt. Moreover, overexpression of mutant Akt, as well as pretreatment with an Akt inhibitor, reduced nanoparticle-specific ERK1/2 phosphorylation, which is decisive for nanoparticle-induced proliferation. With this report, we describe the activation of a pathway by carbon nanoparticles that was so far known to be triggered by ligand receptor binding or on cell adhesion to extracellular matrix proteins.

scholarly journals EphB6 Regulates TFEB-Lysosomal Pathway and Survival of Disseminated Indolent Breast Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1079
Author(s):  
Manuela Zangrossi ◽  
Patrizia Romani ◽  
Probir Chakravarty ◽  
Colin D.H. Ratcliffe ◽  
Steven Hooper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Lung Epithelial Cells ◽  
Late Relapse ◽  
Alveolar Type ◽  
Type I ◽  
Extrinsic Factors ◽  
Lung Epithelial

Late relapse of disseminated cancer cells is a common feature of breast and prostate tumors. Several intrinsic and extrinsic factors have been shown to affect quiescence and reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining the survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes survival of DDCCs of estrogen receptor-positive (ER+) breast tumors. By using a lung organotypic system and in vivo dissemination assays, here we show that the TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct coculture of DDCCs with alveolar type I-like lung epithelial cells and dissemination in the lung drive lysosomal accumulation and EphB6 induction. EphB6 contributes to survival, TFEB transcriptional activity, and lysosome formation in DDCCs in vitro and in vivo. Furthermore, signaling from EphB6 promotes the proliferation of surrounding lung parenchymal cells in vivo. Our data provide evidence that EphB6 is a key factor in the crosstalk between disseminated dormant cancer cells and the lung parenchyma and that the TFEB-lysosomal pathway plays an important role in the persistence of DDCCs.

A noninducible cystine transport system in rat alveolar type II cells

1995 ◽  
Vol 268 (1) ◽  
pp. L21-L26 ◽  
Author(s):  
D. M. Bukowski ◽  
S. M. Deneke ◽  
R. A. Lawrence ◽  
S. G. Jenkinson
Keyword(s):  
Transport System ◽  
Cell Types ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lung Epithelial ◽  
Sodium Dependent ◽  
Type Ii Cell ◽  
Rate Limiting

Type II lung epithelial cells are different from other lung cell types in their means of processing and regulating intracellular glutathione (GSH) levels. In lung cell types, including endothelial cells, fibroblasts, smooth muscle cells, and macrophages, oxidants, sulfhydryl reagents, and electrophilic agents have been shown to induce cystine uptake and concomitantly increase GSH levels, suggesting that cysteine, formed by intracellular reduction of cystine, is a rate-limiting substrate for GSH synthesis. The cystine transport increase was reportedly due to increase in activity of a sodium-independent transport system designated xc-. We have now examined cultures of rat lung type II cells exposed to diethylmaleic acid and arsenite. Although a rise in cellular GSH occurred, cystine transport was not induced. Cystine transport in type II cells was found to differ from the xc- system previously described. Type II cell cystine transport is primarily sodium dependent and is inhibitable by aspartate as well as glutamate and homocysteate. We conclude that the type II cell differs from other lung cell types in both its cystine transport mechanism and method of GSH regulation.

Differentiation of Lung Epithelial Cells from Murine Embryonic Stem Cells with in Vivo Implantation

2013 ◽  
Vol 1 (1) ◽  
pp. 1
Author(s):  
Christine Finck ◽  
Blair Roszell ◽  
Todd Jensen ◽  
Ariel Seaton ◽  
Fan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Epithelial Cells ◽  
Embryonic Stem ◽  
Lung Epithelial Cells ◽  
Murine Embryonic Stem Cells ◽  
Lung Epithelial

scholarly journals EphB6 regulates TFEB-lysosomal pathway and survival of disseminated quiescent breast cancer cells

2020 ◽  
Author(s):  
Manuela Zangrossi ◽  
Probir Chakravarty ◽  
Patrizia Romani ◽  
Colin D.H. Ratcliffe ◽  
Steven Hooper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Lung Epithelial Cells ◽  
Late Relapse ◽  
Alveolar Type ◽  
Type I ◽  
Extrinsic Factors ◽  
Lung Epithelial

AbstractLate relapse of disseminated cancer cells is a common feature of some types of tumors. Several intrinsic and extrinsic factors have been shown to affect reawakening of disseminated dormant cancer cells (DDCCs); however, the signals and processes sustaining survival of DDCCs in a foreign environment are still poorly understood. We have recently shown that crosstalk with lung epithelial cells promotes persistence of DDCCs from estrogen receptor positive (ER+) breast tumors. Here we show that TFEB-lysosomal axis is activated in DDCCs and that it is modulated by the pro-survival ephrin receptor EphB6. TFEB lysosomal direct targets are enriched in DDCCs in vivo and correlate with relapse in ER+ breast cancer patients. Direct contact of DDCCs with alveolar type I-like lung epithelial cells drives lysosomal accumulation and EphB6 induction. EphB6 contributes to TFEB transcriptional activity and lysosome formation in DDCCs in vitro and in vivo, and supports survival of DDCCs in coculture and in vivo. Furthermore, signaling from EphB6 promotes the proliferative response of surrounding lung parenchymal cells in vivo.

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