|
| Status |
Public on Jan 21, 2022 |
| Title |
RNA sequencing of control and PTPN2 knocked down transcriptomes in EndoC-𝛽H1 cells with or without the treatment of pro-inflammatory cytokines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Type 1 diabetes (T1D) results from autoimmune destruction of β-cells in the pancreas. Protein tyrosine phosphatases (PTPs) are candidate genes for T1D and play a key role in autoimmune disease development and β-cell function. Here, we assessed the global protein and individual PTP profile in the pancreas from diabetic NOD mice treated with anti-CD3 monoclonal antibody and IL-1 receptor antagonist (IL-1RA). The treatment reversed hyperglycemia compared to the anti-CD3 alone control group. We observed enhanced expression of PTPN2, a T1D candidate gene, and endoplasmic reticulum (ER) chaperones in islets from mice with reversed diabetes. To address the functional role of PTPN2 in β-cells, we generated PTPN2 deficient stem cell-derived β-like and human EndoC-βH1 cells. Mechanistically, we demonstrated that PTPN2 inactivation in β-cells exacerbates the type I and type II IFN signalling networks, and the potential progression towards autoimmunity. Moreover, we established the capacity of PTPN2 to modulate the Ca2+-dependent unfolded protein response in β-cells. Adenovirus-induced overexpression of PTPN2 decreased BiP expression and partially protected from ER-stress induced β-cell death. Our results postulate PTPN2 as a key protective factor in β-cells during inflammation and ER stress in autoimmune diabetes.
|
| |
|
| Overall design |
mRNA profiles of control and PTPN2 knocked down 𝛽-cells with or without treatment of human interferon-𝛾 or interferon-α
|
| |
|
| Contributor(s) |
Elvira B, Vandenbempt V, Martinez JB, Negueruela J, Vekeriotaite B, Pal SS, Rossello F, Lybaert P, Otonkoski T, Wu W, Gysemans C, Gurzov E |
| Citation(s) |
35044456 |
| |
| Submission date |
Apr 15, 2021 |
| Last update date |
Apr 22, 2022 |
| Contact name |
Valerie Vandenbempt |
| E-mail(s) |
Valerie.vandenbempt@ulb.be
|
| Phone |
0032497208111
|
| Organization name |
Université Libre de Bruxelles
|
| Lab |
Signal Transduction and Metabolism Laboratory
|
| Street address |
Lenniksebaan 808
|
| City |
Anderlecht |
| State/province |
Vlaams-Brabant |
| ZIP/Postal code |
1070 |
| Country |
Belgium |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (18)
|
|
| Relations |
| BioProject |
PRJNA722250 |
| SRA |
SRP314960 |
Less...
More...