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The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis

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Abstract

Dermal mesenchymal stem cells (DMSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation, which were reported to induce the proliferation of keratinocytes, however the regulation on keratinocytes apoptosis was unknown. In this study, we isolated DMSCs from normal skin and co-cultured with keratinocytes, and then detected apoptosis of keratinocytes by flow cytometry and expression of apoptosis associated proteins by western blot. The mRNA expression profile of normal DMSCs was investigated by RNA sequencing. The results of our study presented that the DMSCs promoted HaCaT cells apoptosis both in early apoptotic state (13.8 vs. 2.9, p < 0.05) and late apoptotic state (4.2 vs. 0.7, p < 0.05). The expression of apoptosis associated proteins caspase-3 (3.51 vs. 1.99, p < 0.05) and lymphoid enhancer-binding factor 1 (3.10 vs. 0.83, p < 0.05) were upregulated. However, the cell cycle protein cyclin E1 was similar (9.38 vs. 9.05, p > 0.05). Moreover, 33 genes with the function of induced cell apoptosis were highly expressed in DMSCs, including insulin-like growth factor-binding protein 4 (2828.13), IGFBP7 (1805.69), cathepsin D (1694.34), cathepsin B (CTSB, 1641.40) and dickkopf WNT signaling pathway inhibitor 1 (DKK1, 384.79). This study suggested DMSCs induce the apoptosis of keratinocytes through non-G1/S phase blockade via highly expression of apoptosis inducer.

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Funding

The authors are grateful for funding from the National Natural Science Foundation of China (Nos. 81773336, 81401360). The funding was attributed to the design of the study and the collection, analysis, and interpretation of data.

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Authors and Affiliations

  1. Shanxi Key Laboratory of Stem Cells for Immunological Dermatosis, Institute of Dermatology, Taiyuan Central Hospital of Shanxi Medical University, No. 5 East Third Lane, Jiefang Road, Taiyuan, 030009, Shanxi, China

    Peng An, Jianxiao Xing, Aihong Peng, Xincheng Zhao, Wenjuan Chang, Nannan Liang, Yue Cao, Juan Li, Junqin Li, Ruixia Hou, Xinhua Li & Kaiming Zhang

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  1. Peng An
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  2. Jianxiao Xing
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  3. Aihong Peng
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  4. Xincheng Zhao
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  5. Wenjuan Chang
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  6. Nannan Liang
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  7. Yue Cao
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  8. Juan Li
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  9. Junqin Li
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  10. Ruixia Hou
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  11. Xinhua Li
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  12. Kaiming Zhang
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Contributions

PA and KMZ made substantial contributions to the conception; JXX, AHP, XCZ, WJC, NNL, YC and JL made the acquisition and analysis of data; PA and JXX drafted the work; JQL, RXH and XHL revised the work critically for important intellectual content; KMZ agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy. All authors approved the version to be published.

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Correspondence to Kaiming Zhang.

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An, P., Xing, J., Peng, A. et al. The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis. Cell Tissue Bank 22, 57–65 (2021). https://doi.org/10.1007/s10561-020-09865-w

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  • DOI: https://doi.org/10.1007/s10561-020-09865-w

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