TY - JOUR
T1 - C-Kit and stem cell factor regulate PANC-1 cell differentiation into insulin-and glucagon-producing cells
AU - Wu, Yuexiu
AU - Li, Jinming
AU - Saleem, Saira
AU - Yee, Siu Pok
AU - Hardikar, Anandwardhan A.
AU - Wang, Rennian
PY - 2010/9
Y1 - 2010/9
N2 - Recent evidence has shown that stem cell factor (SCF) and its receptor, c-Kit, have an important role in pancreatic islet development by promoting islet cell differentiation and proliferation. In this study, we examined the role of c-Kit and SCF in the differentiation and proliferation of insulin- and glucagon-producing cells using a human pancreatic duct cell line (PANC-1). Our study showed that increased expression of endocrine cell markers (such as insulin and glucagon) and transcription factors (such as PDX-1 and PAX-6) coincided with a decrease in CK19 and c-Kit cells (P0.001) during PANC-1 cell differentiation, determined by immunofluorescence and qRT-PCR. Cells cultured with exogenous SCF showed an increase in insulin (26%) and glucagon (35%) cell differentiation (P0.01), an increase in cell proliferation (P0.05) and a decrease in cell apoptosis (P0.01). siRNA knockdown of c-Kit resulted in a decrease in endocrine cell differentiation with a reduction in PDX-1 and insulin mRNA, as well as the number of cells immunostaining for PDX-1 and insulin. Taken together, these results show that c-Kit/SCF interactions are involved in mediating islet-like cluster formation and islet-like cell differentiation in a human pancreatic duct cell line.
AB - Recent evidence has shown that stem cell factor (SCF) and its receptor, c-Kit, have an important role in pancreatic islet development by promoting islet cell differentiation and proliferation. In this study, we examined the role of c-Kit and SCF in the differentiation and proliferation of insulin- and glucagon-producing cells using a human pancreatic duct cell line (PANC-1). Our study showed that increased expression of endocrine cell markers (such as insulin and glucagon) and transcription factors (such as PDX-1 and PAX-6) coincided with a decrease in CK19 and c-Kit cells (P0.001) during PANC-1 cell differentiation, determined by immunofluorescence and qRT-PCR. Cells cultured with exogenous SCF showed an increase in insulin (26%) and glucagon (35%) cell differentiation (P0.01), an increase in cell proliferation (P0.05) and a decrease in cell apoptosis (P0.01). siRNA knockdown of c-Kit resulted in a decrease in endocrine cell differentiation with a reduction in PDX-1 and insulin mRNA, as well as the number of cells immunostaining for PDX-1 and insulin. Taken together, these results show that c-Kit/SCF interactions are involved in mediating islet-like cluster formation and islet-like cell differentiation in a human pancreatic duct cell line.
UR - http://www.scopus.com/inward/record.url?scp=77956248555&partnerID=8YFLogxK
U2 - 10.1038/labinvest.2010.106
DO - 10.1038/labinvest.2010.106
M3 - Article
C2 - 20531294
AN - SCOPUS:77956248555
SN - 0023-6837
VL - 90
SP - 1373
EP - 1384
JO - Laboratory Investigation
JF - Laboratory Investigation
IS - 9
ER -
