OASIS/CREB3L1 induces expression of genes involved in extracellular matrix production but not classical endoplasmic reticulum stress response genes in pancreatic beta-cells.
Old astrocyte specifically induced substance (OASIS) has previously been shown to be a putative endoplasmic reticulum (ER) stress sensor in astrocytes with a mechanism of activation that is similar to ATF6. In this study we investigated the expression and activation of endogenous and overexpressed OASIS in pancreatic beta-cells. OASIS mRNA expression was detected in pancreatic beta-cell lines and rodent islets, and the expression level was up-regulated by ER stress-inducing compounds. Endogenous OASIS protein, however, is expressed at low levels in pancreatic beta-cell lines and rodent islets, possibly due to abundant levels of the micro-RNA miR-140 present in these cells. In contrast, expression of both full-length and cleaved (active) OASIS was readily detectable in the developing mouse pancreas (embryonic d 15.5). Microarray analysis after expression of an active nuclear-localized version of OASIS in an inducible INS-1 beta-cell line resulted in the up-regulation of many genes implicated in extracellular matrix production and protein transport but not classical ER stress response genes. Consistent with this, expression of active OASIS failed to induce glucose-regulated protein 78 kDa promoter activity in pancreatic beta-cells. These results suggest that the repertoire of genes induced by OASIS is cell type-dependent and that the OASIS protein may have a role in pancreas development.
Vellanki
Ravi N
RN
Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada M5G1L7.
Zhang
Liling
L
Guney
Michelle A
MA
Rocheleau
Jonathan V
JV
Gannon
Maureen
M
Volchuk
Allen
A
D017398:Alternative Splicing; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D020869:Gene Expression Profiling; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000196:embryology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C552423:CREB3L1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D008156:Luciferases