Alveolar epithelial cell type II as main target of SARS-CoV-2 virus and COVID-19 development via NF-Kb pathway deregulation: A physio-pathological theory

Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.

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Sirtuin3 ameliorates lung senescence and improves type II alveolar epithelial cell function by enhancing the FoxO3a-dependent antioxidant defence mechanism

Stem Cells and Development ◽

10.1089/scd.2021.0099 ◽

2021 ◽

Author(s):

jianxin chen ◽

lei yang ◽

Lu Sun ◽

Wei Chen ◽

jie wu ◽

...

Keyword(s):

Epithelial Cell ◽

Cell Function ◽

Alveolar Epithelial Cell ◽

Type Ii ◽

Defence Mechanism ◽

Antioxidant Defence ◽

Alveolar Epithelial

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Role of collagenase in mediating in vitro alveolar epithelial wound repair

Journal of Cell Science ◽

10.1242/jcs.112.2.243 ◽

1999 ◽

Vol 112 (2) ◽

pp. 243-252

Author(s):

E. Planus ◽

S. Galiacy ◽

M. Matthay ◽

V. Laurent ◽

J. Gavrilovic ◽

...

Keyword(s):

Cell Migration ◽

Cell Adhesion ◽

Epithelial Cell ◽

Type I Collagen ◽

Alveolar Epithelial Cell ◽

Cell Monolayer ◽

Type I ◽

Type Ii ◽

Alveolar Epithelial

Type II pneumocytes are essential for repair of the injured alveolar epithelium. The effect of two MMP collagenases, MMP-1 and MMP-13 on alveolar epithelial repair was studied in vitro. The A549 alveolar epithelial cell line and primary rat alveolar epithelial cell cultures were used. Cell adhesion and cell migration were measured with and without exogenous MMP-1. Wound healing of a cell monolayer of rat alveolar epithelial cell after a mechanical injury was evaluated by time lapse video analysis. Cell adhesion on type I collagen, as well as cytoskeleton stiffness, was decreased in the presence of exogenous collagenases. A similar decrease was observed when cell adhesion was tested on collagen that was first incubated with MMP-1 (versus control on intact collagen). Cell migration on type I collagen was promoted by collagenases. Wound healing of an alveolar epithelial cell monolayer was enhanced in the presence of exogenous collagenases. Our results suggest that collagenases could modulate the repair process by decreasing cell adhesion and cell stiffness, and by increasing cell migration on type I collagen. Collagen degradation could modify cell adhesion sites and collagen degradation peptides could induce alveolar type II pneumocyte migration. New insights regarding alveolar epithelial cell migration are particularly relevant to investigate early events during alveolar epithelial repair following lung injury.

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Cell cycle kinetics in the alveolar epithelium

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1997.272.6.l1031 ◽

1997 ◽

Vol 272 (6) ◽

pp. L1031-L1045 ◽

Cited By ~ 62

Author(s):

B. D. Uhal

Keyword(s):

Epithelial Cell ◽

Alveolar Epithelial Cell ◽

Alveolar Epithelium ◽

Cell Loss ◽

Type Ii ◽

Alveolar Epithelial ◽

Pathological Conditions ◽

Type Ii Cell ◽

The Relationship

The type II alveolar epithelial cell has important metabolic and biosynthetic functions but also serves as the stem cell of the alveolar epithelium. Much of the evidence underlying this premise was obtained before 1980 and provided the basis for a working model that has not been reconsidered for more than fifteen years. With the exceptions to be discussed below, little evidence has accumulated in the interim to suggest that the model requires significant alteration. Important questions remain unanswered, however, and some components of the model need to be supplemented, particularly in light of recent investigations that have provided insights not possible in earlier work. In particular, in vitro studies have suggested that the relationship between the parent type II cell and its progeny may not be as straightforward as originally thought. In addition, the rate of epithelial cell loss was recognized long ago to be an important factor in the regulation of this system, but its kinetics and mechanisms have received little attention. These and other unresolved issues are critical to our understanding of the homeostasis of the alveolar epithelium under normal and pathological conditions.

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Regulation of transport across pulmonary alveolar epithelial cell monolayers

Journal of Applied Physiology ◽

10.1152/jappl.1984.57.3.703 ◽

1984 ◽

Vol 57 (3) ◽

pp. 703-710 ◽

Cited By ~ 51

Author(s):

B. E. Goodman ◽

S. E. Brown ◽

E. D. Crandall

Keyword(s):

Epithelial Cell ◽

Alveolar Epithelial Cell ◽

Phosphodiesterase Inhibitors ◽

Beta Agonist ◽

Type Ii ◽

Dome Formation ◽

Cell Monolayers ◽

Cyclic Monophosphate ◽

Alveolar Epithelial ◽

Epithelial Cell Monolayers

Domes are formed in large numbers by primary cultured monolayers of type II alveolar epithelial cells from rat lungs. These fluid-filled structures are formed by active transport of solute from medium to substratum, with water following passively. In the present study, we used dome-forming monolayers to study the regulation of alveolar epithelial transport processes by determining the effects on dome formation of adenosine 3',5'-cyclic monophosphate (cAMP) analogues, phosphodiesterase inhibitors, neurotransmitters, and vasopressin (antidiuretic hormone, ADH). The cAMP analogues (dibutyryl cAMP and 8-bromo-cAMP) and phosphodiesterase inhibitors (theophylline, papaverine, and isobutylmethylxanthine) caused large increases in dome formation by 24 h. ADH and beta-adrenergic agonists (epinephrine, terbutaline, and isoproterenol) also caused significant increases in dome density. The beta-agonist response was completely eliminated in the presence of the beta-blocker propranolol. Dibutyryl guanosine 3',5'-cyclic monophosphate and acetylcholine (cholinergic agonist) had no effect on dome formation, whereas the alpha-adrenergic agonist methoxamine caused a small but significant decrease in dome formation. These findings suggest that the active solute flux resulting in dome formation by type II alveolar epithelial cell monolayers is increased by substances expected to elevate intracellular cAMP (or analogue) concentrations. An attractive speculation having major implications for lung fluid balance is that transepithelial fluxes can be modulated by endogenous, and perhaps exogenous, chemical agents in adult mammalian alveolar epithelium in vivo.

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