The regulation of dermal mesenchymal stem cells on keratinocytes apoptosis

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.