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2015 ; 10
(7
): e0134092
Nephropedia Template TP
gab.com Text
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English Wikipedia
Partially Evoked Epithelial-Mesenchymal Transition (EMT) Is Associated with
Increased TGF? Signaling within Lesional Scleroderma Skin
#MMPMID26217927
Nikitorowicz-Buniak J
; Denton CP
; Abraham D
; Stratton R
PLoS One
2015[]; 10
(7
): e0134092
PMID26217927
show ga
The origin of myofibroblasts in fibrotic conditions remains unknown and in
systemic sclerosis (SSc) it has been proposed that activation of local
fibroblasts, trans-differentiation of perivascular or vascular cells, recruitment
of fibrocyte progenitors, or epithelial to mesenchymal transition (EMT) could be
contributing. Data from our laboratory indicate that the epidermis in scleroderma
is activated with the keratinocytes exhibiting a phenotype normally associated
with tissue repair, including phosphorylation profiles indicative of TGF?
signaling. Since TGF? is a known inducer of EMT, we investigated if there is
evidence of this process in the SSc epidermis. In order to validate antibodies
and primers, EMT was modeled in HaCaT cells cultured in the presence of TGF?1.
Skin sections were stained with phosho-SMAD2/3, as well as with epithelial and
mesenchymal markers. Moreover, mRNA levels of transcription factors associated
with EMT were studied in epidermal blister sheets. We observed critical changes
in the scleroderma epidermis; showing significantly increased nuclear
translocation of phosphorylated Smad2/3, consistent with active TGF? signaling in
SSc keratinocytes. While profound EMT could be induced in keratinocytes in vitro
with the appearance of SNAI1/2 and FSP-1, and an accompanying loss of E-cadherin,
in the scleroderma skin active TGF? signaling was accompanied by only partial
EMT-like changes characterised by induction of SNAI1 alone and with no loss of
E-cadherin. Together, our findings support a model of altered differentiation and
TGF? dependent activation of scleroderma epithelial cells leading to a partially
evoked EMT like process in the fibrotic skin.