PTPN2, a candidate gene for type 1 diabetes, modulates pancreatic β-cell apoptosis via regulation of the BH3-only protein Bim.

ABSTRACT:

Objective

Genome-wide association studies allowed the identification of several associations between specific loci and type 1 diabetes (T1D). However, the mechanisms by which most candidate genes predispose to T1D remain unclear. We presently evaluated the mechanisms by which PTPN2, a candidate gene for T1D, modulates β-cell apoptosis after exposure to type I and II interferons (IFNs), cytokines that contribute to β-cell loss in early T1D.

Research design and methods

Small interfering RNAs were used to inhibit PTPN2, STAT1, Bim, and Jun NH(2)-terminal kinase 1 (JNK1) expression. Cell death was assessed by Hoechst and propidium iodide staining. BAX translocation, Bim phosphorylation, cytochrome c release, and caspases 9 and 3 activation were measured by Western blot or immuno

SUBMITTER: Santin I 

PROVIDER: S-EPMC3219938 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature