c-Kit and stem cell factor regulate PANC-1 cell differentiation into insulin- and glucagon-producing cells.
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 (P<0.001) 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 (P<0.01), an increase in cell proliferation (P<0.05) and a decrease in cell apoptosis (P<0.01). 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.
Wu
Yuexiu
Y
Children's Health Research Institute, University of Western Ontario, London, ON, Canada.
Li
Jinming
J
Saleem
Saira
S
Yee
Siu-Pok
SP
Hardikar
Anandwardhan A
AA
Wang
Rennian
R
D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D005934:Glucagon / Q000235:genetics / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000737:chemistry / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010183:Pancreatic Ducts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D019089:Stem Cell Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D006728:Hormones; D007328:Insulin; D012333:RNA, Messenger; D019089:Stem Cell Factor; D014157:Transcription Factors; D005934:Glucagon