title: A critical role for the neural zinc factor ST18 in pancreatic β-cell apoptosis.
abstract: The tumor suppressor gene ST18 was originally characterized as the third member of the neural zinc finger transcription factor family. However, little is known about its biological functions. Herein, we demonstrate that, in the pancreas, ST18 expression is restricted to endocrine cells. The detection of ST18 expression in pancreatic β-cells prompted us to investigate its regulation and its role in β-cell mass and function. We show that ST18 expression and activity are increased by cytotoxic concentrations of fatty acids and cytokines in INS832/13 cells. Furthermore, ST18 is also increased in islets of diet-induced obese animals. Overexpression and RNA interference knockdown studies demonstrate that ST18 induces β-cell apoptosis and curtails β-cell replication. Finally, our data suggest that ST18 impairs insulin secretion. Taken together, our findings indicate that ST18 could represent a novel transcriptional mediator of lipotoxicity and cytokine-induced β-cell death. We suggest that genetic or pharmacologic manipulations of ST18 could help maintain a functional β-cell mass.
authors: From the Université Laval and the CRIUCPQ, Quebec G1V 4G5, Canada and.
authors: Cyndi
authors: C
authors: Henry
authors: Anne-Françoise
authors: AF
authors: Close
authors: Jean
authors: J
authors: Buteau
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C497230:ST18 protein, human; C110961:ST18 protein, rat; D014157:Transcription Factors
keywords: Apoptosis; Beta Cell; Insulin Secretion; Lipotoxicity; Obesity; Zinc Finger