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Mesenchymal stem cell (MSC)-mediated survival of insulin producing pancreatic β-cells during cellular stress involves signalling via Akt and ERK1/2.

Abstract：

:Mesenchymal stem cells (MSC) are of interest for cell therapy since their secreted factors mediate immunomodulation and support tissue regeneration. This study investigated the direct humoral interactions between MSC and pancreatic β-cells using human telomerase-immortalized MSC (hMSC-TERT) and rat insulinoma-derived INS-1E β-cells. hMSC-TERT supported survival of cocultured INS-1E β-cells during cellular stress by alloxan (ALX) and streptozotocin (STZ), but not in response to IL-1β. Accordingly, hMSC-TERT had no effect on inflammatory cytokine-related signalling via NF-kB and p-JNK but maintained p-Akt and upregulated p-ERK1/2. Inhibition of either p-Akt or p-ERK1/2 did not abolish protection by hMSC-TERT but activated the respective non-inhibited pathway. This suggests that one pathway compensates for the other. Main results were confirmed in mouse islets except hMSC-TERT-mediated upregulation of p-ERK1/2. Therefore, MSC promote β-cell survival by preservation of p-Akt signalling and further involve p-ERK1/2 activation in certain conditions such as loss of p-Akt or insulinoma background.

journal_name

Mol Cell Endocrinol

journal_title

Molecular and cellular endocrinology

authors

Liu C,Zhang W,Peradze N,Lang L,Straetener J,Feilen PJ,Alt M,Jäger C,Laubner K,Perakakis N,Seufert J,Päth G

doi

10.1016/j.mce.2018.01.024

subject

Has Abstract

pub_date

2018-09-15 00:00:00

pages

235-244

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(18)30047-9

journal_volume

473

pub_type

杂志文章

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