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.

真皮间充质干细胞（DMSCs）是具有自我更新、多向分化和免疫调节能力的祖细胞，据报道可诱导角质形成细胞的增殖，但对角质形成细胞凋亡的调节作用尚不清楚。在本研究中，我们从正常皮肤中分离出 DMSCs 并与角质形成细胞共培养，然后通过流式细胞术检测角质形成细胞的凋亡，并通过蛋白质印迹法检测凋亡相关蛋白的表达。通过RNA测序研究正常DMSCs的mRNA表达谱。我们的研究结果表明，DMSCs 在早期凋亡状态（13.8 对 2.9，p  < 0.05）和晚期凋亡状态（4.2 对 0.7，p < 0.05)。凋亡相关蛋白 caspase-3 (3.51 vs. 1.99, p  < 0.05) 和淋巴增强子结合因子 1 (3.10 vs. 0.83, p  < 0.05) 的表达上调。然而，细胞周期蛋白细胞周期蛋白 E1 是相似的（9.38 对 9.05，p  > 0.05）。此外，33个具有诱导细胞凋亡功能的基因在DMSCs中高表达，包括胰岛素样生长因子结合蛋白4（2828.13）、IGFBP7（1805.69）、组织蛋白酶D（1694.34）、组织蛋白酶B（CTSB，1641.40）和dickkopf WNT 信号通路抑制剂 1 (DKK1, 384.79)。该研究表明，DMSCs 通过高表达凋亡诱导剂，通过非 G1/S 期阻断诱导角质形成细胞凋亡。