Abstract |
The type 1 diabetes (T1D) risk locus on chromosome 15q25.1 harbors the candidate gene CTSH ( cathepsin H). We previously demonstrated that CTSH regulates β-cell function in vitro and in vivo. CTSH overexpression protected insulin-secreting INS-1 cells against cytokine-induced apoptosis. The purpose of the present study was to identify the genes through which CTSH mediates its protective effects. Microarray analysis identified 63 annotated genes differentially expressed between CTSH-overexpressing INS-1 cells and control cells treated with interleukin-1β and interferon-γ for up to 16h. Permutation test identified 10 significant genes across all time-points: Elmod1, Fam49a, Gas7, Gna15, Msrb3, Nox1, Ptgs1, Rac2, Scn7a and Ttn. Pathway analysis identified the " Inflammation mediated by chemokine and cytokine signaling pathway" with Gna15, Ptgs1 and Rac2 as significant. Knockdown of Rac2 abolished the protective effect of CTSH overexpression on cytokine-induced apoptosis, suggesting that the small GTPase and T1D candidate gene Rac2 contributes to the anti-apoptotic effect of CTSH.
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Authors | Tina Fløyel, Aashiq Hussain Mirza, Simranjeet Kaur, Caroline Frørup, Reza Yarani, Joachim Størling, Flemming Pociot |
Journal | Molecular and cellular endocrinology
(Mol Cell Endocrinol)
Vol. 518
Pg. 110993
(12 01 2020)
ISSN: 1872-8057 [Electronic] Ireland |
PMID | 32814070
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Cytokines
- Cathepsin H
- rac GTP-Binding Proteins
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Topics |
- Animals
- Apoptosis
(drug effects, genetics)
- Cathepsin H
(genetics, physiology)
- Cells, Cultured
- Cytokines
(pharmacology)
- Cytoprotection
(drug effects, genetics)
- Humans
- Insulin-Secreting Cells
(drug effects, physiology)
- Mice
- Rats
- rac GTP-Binding Proteins
(physiology)
- RAC2 GTP-Binding Protein
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