Tcf19 is a novel islet factor necessary for proliferation and survival in the INS-1 β-cell line. Am J Physiol Endocrinol Metab 2013 Sep 01;305(5):E600-10
Date
07/19/2013Pubmed ID
23860123Pubmed Central ID
PMC3761170DOI
10.1152/ajpendo.00147.2013Scopus ID
2-s2.0-84883759372 (requires institutional sign-in at Scopus site) 28 CitationsAbstract
Recently, a novel type 1 diabetes association locus was identified at human chromosome 6p31.3, and transcription factor 19 (TCF19) is a likely causal gene. Little is known about Tcf19, and we now show that it plays a role in both proliferation and apoptosis in insulinoma cells. Tcf19 is expressed in mouse and human islets, with increasing mRNA expression in nondiabetic obesity. The expression of Tcf19 is correlated with β-cell mass expansion, suggesting that it may be a transcriptional regulator of β-cell mass. Increasing proliferation and decreasing apoptotic cell death are two strategies to increase pancreatic β-cell mass and prevent or delay diabetes. siRNA-mediated knockdown of Tcf19 in the INS-1 insulinoma cell line, a β-cell model, results in a decrease in proliferation and an increase in apoptosis. There was a significant reduction in the expression of numerous cell cycle genes from the late G1 phase through the M phase, and cells were arrested at the G1/S checkpoint. We also observed increased apoptosis and susceptibility to endoplasmic reticulum (ER) stress after Tcf19 knockdown. There was a reduction in expression of genes important for the maintenance of ER homeostasis (Bip, p58(IPK), Edem1, and calreticulin) and an increase in proapoptotic genes (Bim, Bid, Nix, Gadd34, and Pdia2). Therefore, Tcf19 is necessary for both proliferation and survival and is a novel regulator of these pathways.
Author List
Krautkramer KA, Linnemann AK, Fontaine DA, Whillock AL, Harris TW, Schleis GJ, Truchan NA, Marty-Santos L, Lavine JA, Cleaver O, Kimple ME, Davis DBAuthor
Nathan A. Truchan PhD Research Scientist I in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsCell Cycle
Cell Line, Tumor
Cell Survival
Diabetes Mellitus
Endoplasmic Reticulum Stress
Humans
In Situ Hybridization
Insulin-Secreting Cells
Male
Mice
Mice, Inbred C57BL
RNA
RNA, Small Interfering
Real-Time Polymerase Chain Reaction
Transcription Factors
