OASIS/CREB3L1 induces expression of genes involved in extracellular matrix production but not classical endoplasmic reticulum stress response genes in pancreatic beta-cells.

Vellanki RN, Zhang L, Guney MA, Rocheleau JV, Gannon M, Volchuk A
Endocrinology. 2010 151 (9): 4146-57

PMID: 20668028 · PMCID: PMC2940493 · DOI:10.1210/en.2010-0137

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.

MeSH Terms (24)

Alternative Splicing Animals Blotting, Western Cell Line, Tumor Cells, Cultured Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins Endoplasmic Reticulum Extracellular Matrix Gene Expression Profiling Insulin-Secreting Cells Luciferases Male Mice Mice, Inbred C57BL MicroRNAs Microscopy, Fluorescence Oligonucleotide Array Sequence Analysis Pancreas Rats Rats, Wistar Regulatory Factor X Transcription Factors Reverse Transcriptase Polymerase Chain Reaction Transcription Factors

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