MafA regulates expression of genes important to islet beta-cell function.
Insulin transcription factor MafA is unique in being exclusively expressed at the secondary and principal phase of insulin-expressing cell production during pancreas organogenesis and is the only transcriptional activator present exclusively in islet beta-cells. Here we show that ectopic expression of MafA is sufficient to induce a small amount of endogenous insulin expression in a variety of non-beta-cell lines. Insulin mRNA and protein expression was induced to a much higher level when MafA was provided with two other key insulin activators, pancreatic and duodenal homeobox (PDX-1) and BETA2. Potentiation by PDX-1 and BETA2 was entirely dependent upon MafA, and MafA binding to the insulin enhancer region was increased by PDX-1 and BETA2. Treatment with activin A and hepatocyte growth factor induced even larger amounts of insulin in AR42J pancreatic acinar cells, compared with other non-beta endodermal cells. The combination of PDX-1, BETA2, and MafA also induced the expression of other important regulators of islet beta-cell activity. These results support a critical role of MafA in islet beta-cell function.
Matsuoka
Taka-aki
TA
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871 Japan. takaaki@medone.med.osaka-u.ac.jp
Kaneto
Hideaki
H
Stein
Roland
R
Miyatsuka
Takeshi
T
Kawamori
Dan
D
Henderson
Eva
E
Kojima
Itaru
I
Matsuhisa
Munehide
M
Hori
Masatsugu
M
Yamasaki
Yoshimitsu
Y
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D051473:Maf Transcription Factors, Large / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation
D051273:Glucose Transporter Type 2; D007328:Insulin; C485159:MAFA protein, human; D051473:Maf Transcription Factors, Large; C485160:Mafa protein, mouse; D012333:RNA, Messenger; C495680:SLC2A2 protein, human