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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 PLoS+One
2015 ; 10
(10
): e0140352
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Krüppel-Like Factor 4 Overexpression Initiates a Mesenchymal-to-Epithelial
Transition and Redifferentiation of Human Pancreatic Cells following Expansion in
Long Term Adherent Culture
#MMPMID26457418
Muir KR
; Lima MJ
; Docherty HM
; McGowan NW
; Forbes S
; Heremans Y
; Forbes SJ
; Heimberg H
; Casey J
; Docherty K
PLoS One
2015[]; 10
(10
): e0140352
PMID26457418
show ga
A replenishable source of insulin-producing cells has the potential to cure type
1 diabetes. Attempts to culture and expand pancreatic ?-cells in vitro have
resulted in their transition from insulin-producing epithelial cells to
mesenchymal stromal cells (MSCs) with high proliferative capacity but devoid of
any hormone production. The aim of this study was to determine whether the
transcription factor Krüppel-like factor 4 (KLF4), could induce a
mesenchymal-to-epithelial transition (MET) of the cultured cells. Islet-enriched
pancreatic cells, allowed to dedifferentiate and expand in adherent cell culture,
were transduced with an adenovirus containing KLF4 (Ad-Klf4). Cells were
subsequently analysed for changes in cell morphology by light microscopy, and for
the presence of epithelial and pancreatic markers by immunocytochemistry and
quantitative RT/PCR. Infection with Ad-Klf4 resulted in morphological changes,
down-regulation of mesenchymal markers, and re-expression of both epithelial and
pancreatic cell markers including insulin and transcription factors specific to
?-cells. This effect was further enhanced by culturing cells in suspension.
However, the effects of Ad-KLf4 were transient and this was shown to be due to
increased apoptosis in Klf4-expressing cells. Klf4 has been recently identified
as a pioneer factor with the ability to modulate the structure of chromatin and
enhance reprogramming/transdifferentiation. Our results show that Klf4 may have a
role in the redifferentiation of expanded pancreatic cells in culture, but before
this can be achieved the off-target effects that result in increased apoptosis
would need to be overcome.