Transitional human alveolar type II epithelial cells suppress extracellular matrix and growth factor gene expression in lung fibroblasts
| Autor: | Elizabeth F. Redente, Karen E. Edeen, Amanda Mikels-Vigdal, Rachel L. Zemans, Douglas Curran-Everett, Karina A. Serban, Robert J. Mason, Kelly A. Correll, Benjamin L. Edelman |
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| Rok vydání: | 2019 |
| Předmět: |
Pulmonary and Respiratory Medicine
ARDS Physiology Extracellular matrix Response to injury Physiology (medical) Pulmonary fibrosis medicine Humans Lung Cells Cultured FGF10 Alveolar type Chemistry Hepatocyte Growth Factor Epithelial Cells Pulmonary Surfactants Cell Biology Fibroblasts medicine.disease Cell biology Extracellular Matrix medicine.anatomical_structure Alveolar Epithelial Cells Collagen Growth Factor Gene Research Article |
| Zdroj: | Am J Physiol Lung Cell Mol Physiol |
| ISSN: | 1522-1504 |
| Popis: | Epithelial-fibroblast interactions are thought to be very important in the adult lung in response to injury, but the specifics of these interactions are not well defined. We developed coculture systems to define the interactions of adult human alveolar epithelial cells with lung fibroblasts. Alveolar type II cells cultured on floating collagen gels reduced the expression of type 1 collagen (COL1A1) and α-smooth muscle actin (ACTA2) in fibroblasts. They also reduced fibroblast expression of hepatocyte growth factor (HGF), fibroblast growth factor 7 (FGF7, KGF), and FGF10. When type II cells were cultured at an air-liquid interface to maintain high levels of surfactant protein expression, this inhibitory activity was lost. When type II cells were cultured on collagen-coated tissue culture wells to reduce surfactant protein expression further and increase the expression of some type I cell markers, the epithelial cells suppressed transforming growth factor-β (TGF-β)-stimulated ACTA2 and connective tissue growth factor (CTGF) expression in lung fibroblasts. Our results suggest that transitional alveolar type II cells and likely type I cells but not fully differentiated type II cells inhibit matrix and growth factor expression in fibroblasts. These cells express markers of both type II cells and type I cells. This is probably a normal homeostatic mechanism to inhibit the fibrotic response in the resolution phase of wound healing. Defining how transitional type II cells convert activated fibroblasts into a quiescent state and inhibit the effects of TGF-β may provide another approach to limiting the development of fibrosis after alveolar injury. |
| Databáze: | OpenAIRE |
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