Rho Kinase Inhibition Enhances Airway Epithelial Cell Proliferation, Ciliogenesis And Efficiency Of Lentivirus Transfection

Neuropeptides stimulate airway epithelial cell proliferation and migration in vitro, but the role of neuropeptides in the repair of the epithelium after injury in vivo is not clear. We studied epithelial proliferation and repair in 83 male Hartley guinea pigs. Animals received capsaicin weekly for 3 wk to deplete airway neuropeptides. One week later, the dorsal aspect of the trachea was injured with a metal stylette. Animals were killed 1 h to 1 wk later, after which epithelial cell proliferation was assessed for the presence of proliferating cell nuclear antigen (PCNA). PCNA labeling was <3% in noninjured animals. PCNA labeling increased substantially in the first 72 h after injury in control animals but was significantly decreased in capsaicin-treated animals within and adjacent to the site of injury. PCNA labeling increased opposite to the injury site in both control and capsaicin animals over the first 72 h. We conclude that neuropeptide depletion significantly attenuates both epithelial cell proliferation and repair in the first 72 h after mechanical injury to the trachea. However, neuropeptide depletion did not slow the ultimate repair of tracheal mucosal injury. Proliferation of epithelial cells in response to injury occurs throughout the airway, even away from the injury site.

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Cysteinyl leukotrienes enhance growth of human airway epithelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1990.259.4.l255 ◽

1990 ◽

Vol 259 (4) ◽

pp. L255-L261 ◽

Cited By ~ 5

Author(s):

G. D. Leikauf ◽

H. E. Claesson ◽

C. A. Doupnik ◽

S. Hybbinette ◽

R. C. Grafstrom

Keyword(s):

Cell Proliferation ◽

Epithelial Cell ◽

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Epithelial Cell Proliferation ◽

Leukotriene C4 ◽

Cysteinyl Leukotrienes ◽

Human Airway ◽

Human Airway Epithelial Cells

Epithelial inflammation may play an obligatory role in the pathogenesis of a number of chronic pulmonary diseases such as asthma or bronchitis and has been implicated during the promotion phase of multistage carcinogenesis. At sites of inflammation, bioactive lipid mediators are released and activate a wide range of pathophysiological responses including bronchospasm. Previous studies suggest that one class of inflammatory mediators, the eicosanoids, can also influence cell growth. Epithelial cell proliferation and hyperplasia are common sequelae to irritation and inflammation, and because the lung has a high capacity to produce eicosanoids, we investigated the effects of a group of these compounds, the cysteinyl leukotrienes, on growth of human airway epithelial cells. Leukotrienes were found to be mitogenic in a concentration-dependent manner and exhibit a structure-activity relationship, with leukotriene C4 being more potent than its sequential metabolites leukotriene D4 and E4. The potency of leukotriene C4 is striking, stimulating colony-forming efficiency in concentrations as low as 10 fM. These findings suggest a new physiological role for leukotrienes in the lung that links inflammation with epithelial cell proliferation.

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An essential function for autocrine Hedgehog signaling in epithelial proliferation and differentiation in the trachea

10.1101/2022.01.13.476169 ◽

2022 ◽

Author(s):

Wenguang Yin ◽

Andreas Liontos ◽

Janine Koepke ◽

Maroua Ghoul ◽

Luciana Mazzocchi ◽

...

Keyword(s):

Cell Proliferation ◽

Epithelial Cell ◽

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Epithelial Cell Proliferation ◽

Human Airway ◽

Cell Proliferation And Differentiation ◽

Proliferation And Differentiation ◽

Hh Signaling

The tracheal epithelium is a primary target for pulmonary diseases as it provides a conduit for air flow between the environment and the lung lobes. The cellular and molecular mechanisms underlying airway epithelial cell proliferation and differentiation remain poorly understood. Hedgehog (Hh) signaling orchestrates communication between epithelial and mesenchymal cells in the lung, where it modulates stromal cell proliferation, differentiation and signaling back to the epithelium. Here, we reveal a new, autocrine function of Hh signaling in airway epithelial cells. Epithelial cell depletion of the ligand Sonic hedgehog (SHH) or its effector Smoothened (SMO) causes defects in both epithelial cell proliferation and differentiation. In cultured primary human airway epithelial cells, Hh signaling inhibition also hampers cell proliferation and differentiation. Epithelial Hh function is mediated, at least in part, through transcriptional activation as Hh signaling inhibition leads to downregulation of cell-type specific transcription factor genes in both the mouse trachea and human airway epithelial cells. These results provide new insights into the role of Hh signaling in epithelial cell proliferation and differentiation during airway development.

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