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Interleukin-11 regulates the fate of adipose-derived mesenchymal stem cells via STAT3 signalling pathways.

ABSTRACT: OBJECTIVE:Adipose-derived mesenchymal stem cells (ADSCs) offer great promise as cell therapy for ischaemic diseases. Due to their poor survival in the ischaemic environment, the therapeutic efficacy of ADSCs is still relatively low. Interleukin-11 (IL-11) has been shown to play a key role in promoting cell proliferation and protecting cells from oxidative stress injury. The aim of this study was to determine whether IL-11 could improve therapeutic efficacy of ADSCs in ischaemic diseases. METHODS AND RESULTS:ADSCs were prepared from inguinal subcutaneous adipose tissue and exposed to hypoxic environment. The protein expression of IL-11 was decreased after hypoxic treatment. In addition, ADSCs viability was increased after IL-11 treatment under hypoxia. Moreover, IL-11 enhanced ADSCs viability in a dose-dependent manner under normoxia. Importantly, IL-11 promoted ADSCs proliferation and migration and protected ADSCs against hydrogen peroxide-induced cellular death. Notably, IL-11 enhanced ADSCs proliferation and migration, also promoted cell survival and apoptosis resistance by STAT3 signalling. In vivo, mice were subjected to limb ischaemia and treated with IL-11 overexpression ADSCs and control ADSCs. IL-11 overexpression ADSCs improved perfusion recovery in the ischaemic muscles. CONCLUSIONS:We provide the evidence that IL-11 promoted ADSCs proliferation, stimulated ADSCs migration and attenuated ADSCs apoptosis by activation of STAT3 signalling. These results suggest that IL-11 facilitated ADSCs engraftment in ischaemic tissue, thereby enhanced ADSCs therapeutic efficacy.

SUBMITTER: Yang W

PROVIDER: S-EPMC7260062 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Interleukin-11 regulates the fate of adipose-derived mesenchymal stem cells via STAT3 signalling pathways.

Yang Wenlong W Zhang Shuning S Ou Tiantong T Jiang Hao H Jia Daile D Qi Zhiyong Z Zou Yunzeng Y Qian Juying J Sun Aijun A Ge Junbo J

Cell proliferation 20200409 5

<h4>Objective</h4>Adipose-derived mesenchymal stem cells (ADSCs) offer great promise as cell therapy for ischaemic diseases. Due to their poor survival in the ischaemic environment, the therapeutic efficacy of ADSCs is still relatively low. Interleukin-11 (IL-11) has been shown to play a key role in promoting cell proliferation and protecting cells from oxidative stress injury. The aim of this study was to determine whether IL-11 could improve therapeutic efficacy of ADSCs in ischaemic diseases. ...[more]

PMID: 32270546

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Project description:BackgroundHuman adipose-derived stem cells (hADSCs) are stem cells with the potential to differentiate in multiple directions. miR-204-5p is expressed at low levels during the osteogenic differentiation of hADSCs, and its specific regulatory mechanism remains unclear. Here, we aimed to explore the function and possible molecular mechanism of miR-204-5p in the osteogenic differentiation of hADSCs.MethodsThe expression patterns of miR-204-5p, Runx2, alkaline phosphatase (ALP), osteocalcin (OCN), forkhead box C1 (FOXC1) and growth differentiation factor 7 (GDF7) in hADSCs during osteogenesis were detected by qRT-PCR. Then, ALP and alizarin red staining (ARS) were used to detect osteoblast activities and mineral deposition. Western blotting was conducted to confirm the protein levels. The regulatory relationship among miR-204-5p, FOXC1 and GDF7 was verified by dual-luciferase activity and chromatin immunoprecipitation (ChIP) assays.ResultsmiR-204-5p expression was downregulated in hADSC osteogenesis, and overexpression of miR-204-5p suppressed osteogenic differentiation. Furthermore, the levels of FOXC1 and GDF7 were decreased in the miR-204-5p mimics group, which indicates that miR-204-5p overexpression suppresses the expression of FOXC1 and GDF7 by binding to their 3'-untranslated regions (UTRs). Overexpression of FOXC1 or GDF7 improved the inhibition of osteogenic differentiation of hADSCs induced by the miR-204-5p mimics. Moreover, FOXC1 was found to bind to the promoter of miR-204-5p and GDF7, promote the deacetylation of miR-204-5p and reduce the expression of miR-204-5p, thus promoting the expression of GDF7 during osteogenic differentiation. GDF7 induced hADSC osteogenesis differentiation by activating the AKT and P38 signalling pathways.ConclusionsOur results demonstrated that the miR-204-5p/FOXC1/GDF7 axis regulates the osteogenic differentiation of hADSCs via the AKT and p38 signalling pathways. This study further revealed the regulatory mechanism of hADSC differentiation from the perspective of miRNA regulation.

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Interleukin-11 regulates the fate of adipose-derived mesenchymal stem cells via STAT3 signalling pathways.

Publications

Interleukin-11 regulates the fate of adipose-derived mesenchymal stem cells via STAT3 signalling pathways.

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