RRC ID 43047
Author Matsuoka TA, Kaneto H, Stein R, Miyatsuka T, Kawamori D, Henderson E, Kojima I, Matsuhisa M, Hori M, Yamasaki Y.
Title MafA regulates expression of genes important to islet beta-cell function.
Journal Mol Endocrinol
Abstract 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.
Volume 21(11)
Pages 2764-74
Published 2007-11-1
DOI 10.1210/me.2007-0028
PII me.2007-0028
PMID 17636040
MeSH Animals Cell Nucleus / metabolism Gene Expression Regulation* Glucose Transporter Type 2 / metabolism HeLa Cells Humans Insulin / metabolism Insulin-Secreting Cells / metabolism* Islets of Langerhans / metabolism* Maf Transcription Factors, Large / metabolism Maf Transcription Factors, Large / physiology* Mice Models, Biological Protein Binding RNA, Messenger / metabolism Transcriptional Activation
IF 3.628
Times Cited 71
WOS Category ENDOCRINOLOGY & METABOLISM
Resource
Human and Animal Cells IEC 6(RCB0993)