当前位置： SCI文献检索 > MOLECULAR AND CELLULAR ENDOCRINOLOGY期刊下所有文献 > The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells.

The Rac2 GTPase contributes to cathepsin H-mediated protection against cytokine-induced apoptosis in insulin-secreting cells.

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.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Fløyel T,Mirza AH,Kaur S,Frørup C,Yarani R,Størling J,Pociot F

doi

10.1016/j.mce.2020.110993

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

110993

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(20)30295-1

journal_volume

518

pub_type

杂志文章

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