Differential expression of CCAAT enhancer binding protein family in rat alveolar epithelial cell proliferation and in acute lung injury

1999 ◽  
Vol 297 (2) ◽  
pp. 261-270 ◽  
Author(s):  
K. Sugahara ◽  
Tomohiro Sadohara ◽  
Michiko Sugita ◽  
Ken-ichi Iyama ◽  
Masaki Takiguchi
Keyword(s):  
Cell Proliferation ◽  
Acute Lung Injury ◽  
Epithelial Cell ◽  
Lung Injury ◽  
Differential Expression ◽  
Alveolar Epithelial Cell ◽  
Protein Family ◽  
Epithelial Cell Proliferation ◽  
Alveolar Epithelial ◽  
Enhancer Binding Protein

Regulation of type II alveolar epithelial cell proliferation by TGF-beta during bleomycin-induced lung injury in rats

1994 ◽  
Vol 267 (5) ◽  
pp. L498-L507 ◽  
Author(s):  
N. Khalil ◽  
R. N. O'Connor ◽  
K. C. Flanders ◽  
W. Shing ◽  
C. I. Whitman
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Alveolar Epithelial Cell ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Epithelial Cell Proliferation ◽  
Tgf Beta ◽  
Alveolar Epithelial

Three isoforms of transforming growth factor-beta (TGF-beta) are found in mammalian cells and are potent regulators of inflammation, connective tissue synthesis, cellular proliferation, and differentiation. To determine the distribution and regulation of TGF-beta isoforms during pulmonary injury, a rat model of bleomycin-induced lung inflammation and repair was used. Using immunohistochemistry, we demonstrate that TGF-beta 2 and TGF-beta 3 were localized to alveolar macrophages as well as epithelial and smooth muscle cells of both normal rat lungs and rat lungs obtained at all time intervals after bleomycin administration. Early in bleomycin-induced lung injury, when there is active proliferation of type II alveolar epithelial cells, there was an increase in the number of type II alveolar epithelial cells isolated per lung and an increase in DNA synthesis by explanted type II alveolar epithelial cells. At this time, the secretion of biologically active TGF-beta 1–3, which are potent inhibitors of epithelial cell proliferation, was decreased. However, the secretion of TGF-beta 1–3 activity was markedly increased later in the injury response and coincided with a reduction in the number of type II alveolar epithelial cells isolated per lung and DNA synthesis in vitro. Furthermore, the addition of TGF-beta 1, 2, and 3 to cultures of actively proliferating type II alveolar epithelial cells resulted in inhibition of [3H]thymidine incorporation, whereas, in the presence of anti-TGF-beta 1-3 antibody, there was an increase in [3H]thymidine incorporation. Our findings suggest that altered secretion of TGF-beta 1-3 activity by type II alveolar epithelial cells during bleomycin-induced lung injury may regulate pulmonary alveolar epithelial cell proliferation during injury and repair phases.

scholarly journals Senescence of IPF Lung Fibroblasts Disrupt Alveolar Epithelial Cell Proliferation and Promote Migration in Wound Healing

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 389 ◽  
Author(s):  
Kaj E. C. Blokland ◽  
David W. Waters ◽  
Michael Schuliga ◽  
Jane Read ◽  
Simon D. Pouwels ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Wound Repair ◽  
Alveolar Epithelial Cell ◽  
Lung Parenchyma ◽  
Repair Process ◽  
Lung Fibroblasts ◽  
Epithelial Cell Proliferation ◽  
Alveolar Epithelial ◽  
M Phase

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by excessive accumulation of lung fibroblasts (LFs) and collagen in the lung parenchyma. The mechanisms that underlie IPF pathophysiology are thought to reflect repeated alveolar epithelial injury leading to an aberrant wound repair response. Recent work has shown that IPF-LFs display increased characteristics of senescence including growth arrest and a senescence-associated secretory phenotype (SASP) suggesting that senescent LFs contribute to dysfunctional wound repair process. Here, we investigated the influence of senescent LFs on alveolar epithelial cell repair responses in a co-culture system. Alveolar epithelial cell proliferation was attenuated when in co-culture with cells or conditioned media from, senescence-induced control LFs or IPF-LFs. Cell-cycle analyses showed that a larger number of epithelial cells were arrested in G2/M phase when co-cultured with IPF-LFs, than in monoculture. Paradoxically, the presence of LFs resulted in increased A549 migration after mechanical injury. Our data suggest that senescent LFs may contribute to aberrant re-epithelialization by inhibiting proliferation in IPF.

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