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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 J+Biol+Chem
2014 ; 289
(51
): 35503-16
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Hes3 is expressed in the adult pancreatic islet and regulates gene expression,
cell growth, and insulin release
#MMPMID25371201
Masjkur J
; Arps-Forker C
; Poser SW
; Nikolakopoulou P
; Toutouna L
; Chenna R
; Chavakis T
; Chatzigeorgiou A
; Chen LS
; Dubrovska A
; Choudhary P
; Uphues I
; Mark M
; Bornstein SR
; Androutsellis-Theotokis A
J Biol Chem
2014[Dec]; 289
(51
): 35503-16
PMID25371201
show ga
The transcription factor Hes3 is a component of a signaling pathway that supports
the growth of neural stem cells with profound consequences in neurodegenerative
disease models. Here we explored whether Hes3 also regulates pancreatic islet
cells. We showed that Hes3 is expressed in human and rodent pancreatic islets. In
mouse islets it co-localizes with alpha and beta cell markers. We employed the
mouse insulinoma cell line MIN6 to perform in vitro characterization and
functional studies in conditions known to modulate Hes3 based upon our previous
work using neural stem cell cultures. In these conditions, cells showed elevated
Hes3 expression and nuclear localization, grew efficiently, and showed higher
evoked insulin release responses, compared with serum-containing conditions. They
also exhibited higher expression of the transcription factor Pdx1 and insulin.
Furthermore, they were responsive to pharmacological treatments with the GLP-1
analog Exendin-4, which increased nuclear Hes3 localization. We employed a
transfection approach to address specific functions of Hes3. Hes3 RNA
interference opposed cell growth and affected gene expression as revealed by DNA
microarrays. Western blotting and PCR approaches specifically showed that Hes3
RNA interference opposes the expression of Pdx1 and insulin. Hes3 overexpression
(using a Hes3-GFP fusion construct) confirmed a role of Hes3 in regulating Pdx1
expression. Hes3 RNA interference reduced evoked insulin release. Mice lacking
Hes3 exhibited increased islet damage by streptozotocin. These data suggest roles
of Hes3 in pancreatic islet function.