Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein.
Thioredoxin-interacting protein (TXNIP) is overexpressed in diabetes and has deleterious effects on pancreatic beta-cells and the cardiovascular system. TXNIP is a regulator of the cellular redox state, but has also been suggested to act as a transcriptional repressor. However, the genes and pathways regulated by TXNIP remain unknown. We therefore compared gene expression in INS-1 insulinoma beta-cells overexpressing TXNIP and control LacZ-overexpressing cells using the Affymetrix 230A rat chip. Analysis with the Bayes methodology revealed 98 differentially expressed genes, 90 of which were down-regulated, consistent with the predicted role of TXNIP as a repressor. Using the PathwayAssist software, we found that affected genes were involved in cell death/survival and insulin secretion, and confirmed these findings by real-time RT-PCR and by functional studies. Thus, aside from regulating the cellular redox, TXNIP does modulate overall gene transcription and thereby may further enhance beta-cell death and impair insulin secretion.
Minn
Alexandra H
AH
Department of Medicine, University of Wisconsin-Madison, WI, USA.
Pise-Masison
Cynthia A
CA
Radonovich
Michael
M
Brady
John N
JN
Wang
Ping
P
Kendziorski
Christina
C
Shalev
Anath
A
D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma; D007515:Islets of Langerhans / Q000378:metabolism*; D008954:Models, Biological; D010190:Pancreatic Neoplasms; D013879:Thioredoxins / Q000378:metabolism*
D002352:Carrier Proteins; D007328:Insulin; C486715:TXNIP protein, human; D013879:Thioredoxins