OASIS/CREB3L1 Induces Expression of Genes Involved in Extracellular Matrix Production But Not Classical Endoplasmic Reticulum Stress Response Genes in Pancreatic β-Cells

• Published in: Endocrinology (Philadelphia) Vol. 151; no. 9; pp. 4146 - 4157
• Main Authors: Vellanki, Ravi N, Zhang, Liling, Guney, Michelle A, Rocheleau, Jonathan V, Gannon, Maureen, Volchuk, Allen
• Format: Journal Article
• Language: English
• Published: Chevy Chase, MD Endocrine Society 01.09.2010; The Endocrine Society
• Subjects: Alternative Splicing; Animals; Astrocytes; Beta cells; Biological and medical sciences; Blotting, Western; Cell Line, Tumor; Cells, Cultured; Cyclic AMP Response Element-Binding Protein - genetics; Cyclic AMP Response Element-Binding Protein - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Embryos; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Extracellular matrix; Extracellular Matrix - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Insulin-Secreting Cells - cytology; Insulin-Secreting Cells - metabolism; Islets of Langerhans; Luciferases - genetics; Luciferases - metabolism; Male; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Microscopy, Fluorescence; Oligonucleotide Array Sequence Analysis; Pancreas; Pancreas - embryology; Pancreas - metabolism; Promoters; Protein transport; Rats; Rats, Wistar; Regulatory Factor X Transcription Factors; Reverse Transcriptase Polymerase Chain Reaction; Stress; Transcription Factors - genetics; Transcription Factors - metabolism; Vertebrates: endocrinology; Gene; Langerhans islet; Extracellular matrix; β Cell; Gene expression; Endoplasmic reticulum; Stress; Endocrine pancreas
• ISSN: 0013-7227; 1945-7170
• 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 β-cells. OASIS mRNA expression was detected in pancreatic β-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 β-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 β-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 β-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. The endoplasmic reticulum stress sensor, OASIS, induces expression of extracellular matrix genes and may be important in pancreas development.