Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells
Por:
Checa, Marco, Hagood, James S., Velazquez-Cruz, Rafael, Ruiz, Victor, Garcia-De-Alba, Carolina, Rangel-Escareno, Claudia, Urrea, Francisco, Becerril, Carina, Montano, Martha, Garcia-Trejo, Semiramis, Cisneros Lira, Jose, Aquino-Galvez, Arnoldo, Pardo, Annie, Selman, Moises
Publicada:
2 mar 2016
Resumen:
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease
of unknown etiology. A growing body of evidence indicates that it may
result from an aberrant activation of alveolar epithelium, which induces
the expansion of the fibroblast population, their differentiation to
myofibroblasts and the excessive accumulation of extracellular matrix.
The mechanisms that activate the alveolar epithelium are unknown, but
several studies indicate that smoking is the main environmental risk
factor for the development of IPF. In this study we explored the effect
of cigarette smoke on the gene expression profile and signaling pathways
in alveolar epithelial cells. Lung epithelial cell line from human
(A549), was exposed to cigarette smoke extract (CSE) for 1, 3, and 5
weeks at 1, 5 and 10% and gene expression was evaluated by complete
transcriptome microarrays. Signaling networks were analyzed with the
Ingenuity Pathway Analysis software. At 5 weeks of exposure, alveolar
epithelial cells acquired a fibroblast-like phenotype. At this time,
gene expression profile revealed a significant increase of more than
1000 genes and deregulation of canonical signaling pathways such as
TGF-beta and Wnt. Several profibrotic genes involved in EMT were
over-expressed, and incomplete EMT was observed in these cells, and
corroborated in mouse (MLE-12) and rat (RLE-6TN) epithelial cells. The
secretion of activated TGF-beta 1 increased in cells exposed to
cigarette smoke, which decreased when the integrin alpha v gene was
silenced. These findings suggest that the exposure of alveolar
epithelial cells to CSE induces the expression and release of a variety
of profibrotic genes, and the activation of TGF-beta 1, which may
explain at least partially, the increased risk of developing IPF in
smokers.
Filiaciones:
Checa, Marco:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Hagood, James S.:
Univ Calif San Diego, Dept Pediat, Div Resp Med, San Diego, CA 92103 USA
Rady Childrens Hosp San Diego, San Diego, CA USA
Velazquez-Cruz, Rafael:
Inst Nacl Med Genom, Mexico City, DF, Mexico
Ruiz, Victor:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Garcia-De-Alba, Carolina:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Rangel-Escareno, Claudia:
Inst Nacl Med Genom, Mexico City, DF, Mexico
Urrea, Francisco:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Becerril, Carina:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Montano, Martha:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Garcia-Trejo, Semiramis:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Cisneros Lira, Jose:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Aquino-Galvez, Arnoldo:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
Pardo, Annie:
Univ Nacl Autonoma Mexico, Fac Ciencias, Mexico City 04510, DF, Mexico
Selman, Moises:
Inst Nacl Enfermedades Resp, Mexico City, DF, Mexico
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