SNAI transcription factors mediate epithelial--mesenchymal transition in lung fibrosis

SNAI transcription factors mediate epithelial--mesenchymal transition in lung fibrosis

Beschreibung

vor 15 Jahren
Background: Idiopathic pulmonary fibrosis (IPF) is a fatal
interstitial lung disease characterised by accumulation of
activated (myo)fibroblasts and excessive extracellular matrix
deposition. The enhanced accumulation of (myo)fibroblasts may be
attributed, in part, to the process of transforming growth factor
\textgreekb1 (TGF\textgreekb1)-induced epithelial--mesenchymal
transition (EMT), the phenotypic switching of epithelial to
fibroblast-like cells. Although alveolar epithelial type II (ATII)
cells have been shown to undergo EMT, the precise mediators and
mechanisms remain to be resolved. The objective of this study is to
investigate the role of SNAI transcription factors in the process
of EMT and in IPF.Methods: Using quantitative reverse
transcription-PCR (RT-PCR), immunofluorescence,
immunohistochemistry, western blotting, as well as gain- and
loss-of-function studies and functional assays, the role of SNAI1
and SNAI2 in TGF\textgreekb1-induced EMT in ATII cells in vitro was
assessed; and the expression of SNAI transcription factors was
analysed in experimental and human IPF in vivo.Results:
TGF\textgreekb1 treatment increased the expression and nuclear
accumulation of SNAI1 and SNAI2, in concert with induction of EMT
in ATII cells. SNAI overexpression was sufficient to induce EMT,
and small interfering RNA (siRNA)-mediated SNAI depletion
attenuated TGF\textgreekb1-induced ATII cell migration and EMT.
SNAI expression was elevated in experimental and human IPF and
localised to hyperplastic ATII cells in vivo.Conclusions: The
results demonstrate that TGF\textgreekb1-induced EMT in ATII cells
is essentially controlled by the expression and nuclear
translocation of SNAI transcription factors. Increased SNAI1 and
SNAI2 expression in experimental and human IPF in vivo suggests
that SNAI-mediated EMT may contribute to the fibroblast pool in
idiopathic pulmonary fibrosis.

Kommentare (0)

Lade Inhalte...

Abonnenten

15
15
:
: