The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis

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The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis Peng An . Jianxiao Xing . Aihong Peng . Xincheng Zhao . Wenjuan Chang . Nannan Liang . Yue Cao . Juan Li . Junqin Li . Ruixia Hou . Xinhua Li . Kaiming Zhang

Received: 27 April 2020 / Accepted: 18 September 2020 Ó Springer Nature B.V. 2020

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

P. An  J. Xing  A. Peng  X. Zhao  W. Chang  N. Liang  Y. Cao  J. Li  J. Li  R. Hou  X. Li  K. Zhang (&) 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 e-mail: [email protected]

W. Chang e-mail: [email protected]

P. An e-mail: [email protected]

J. Li e-mail: [email protected]

J. Xing e-mail: [email protected]

R. Hou e-mail: [email protected]

A. Peng e-mail: [email protected]

X. Li e-mail: [email protected]

N. Liang e-mail: [email protected] Y. Cao e-mail: [email protected] J. Li e-mail: [email protected]

X. Zhao e-mail: [email protected]

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Cell Tissue Bank

keratinocytes through non-G1/S phase blockade via highly expression of apoptosis inducer.

Materials and methods Samples

Keywords Dermal mesenchymal stem cells  Keratinocytes  Induce  Apoptosis

Introduction Mesenchymal stem cells (MSCs) are progenitor cells with the capacity of self-renewal, multilineage differentiation, and immunomodulation (Li and Hua 2017; Liu et al. 2019). Strikingly, emerging experimental and clinical evidence has shown that systemic infusion of MSCs has significant immunosuppressive effects on the treatment of a variety of inflammatory and autoimmune disease