PBX1抑制H2O2致HF-MSC氧化损伤作用及其机制研究

毛囊间充质干细胞(HF-MSC)是毛囊的主要形成细胞，参与毛发发生、毛囊周期循环、毛囊损伤修复和再生。过氧化氢(H2O2)是氧化型染发剂主要成分之一，具有很强的渗透性，可引起HF-MSC氧化损伤，破坏毛囊微环境，引起毛发脱落。前期工作中，我们在国家自然科学基金资助下，研究发现过表达前B细胞白血病转录因子1(PBX1)，上调聚ADP核糖聚合酶1(PARP1)表达，促进HF-MSC增殖，减缓H2O2致HF-MSC氧化损伤。新近我们又研究发现过表达PBX1、敲减PARP1增加H2O2致HF-MSC氧化损伤，但其中的作用机制不清。鉴于PARP1是DNA损伤响应因子，参与DNA损伤修复。我们推测PBX1可能通过上调PARP1，修复受损的DNA，抑制H2O2致HF-MSC氧化损伤。故本项目主要从DNA损伤修复角度探讨PBX1抑制H2O2致HF-MSC氧化损伤作用机制，为毛发损伤修复和再生提供理论依据。

Hair follicle mesenchymal stem cells (HF-MSC) are the main forming cells of hair follicles and are involved in hair generation, hair follicle cycle, hair follicle repair and regeneration. Hydrogen peroxide (H2O2) is one of the main components of oxidative hair dyes. It has strong perrmeability and can causes HF-MSC oxidative damage, subsequently deteriorates hair follicle microenvironment, and causes hair loss. In our previous work, we showed that overexpression of pre-B-cell leukemia transcription factor1 (PBX1) up-regulated poly ADP ribose polymerase 1 (PARP1) expression, promoted HF-MSC proliferation, and attenuated H2O2.induced oxidative damage to HF-MSC. In our recent work we have also found that PBX1 overexpression and PARP1 knockdown increases H2O2-induced oxidative damage to HF-MSC, but the mechanism laying behind this phenomenon is unclear. Given that PARP1 is a DNA damage response factor, and is involved in DNA damage repair. We speculate that PBX1 may inhibit H2O2-induced oxidative damage to HF-MSC by repair of DNA damage. Therefore, this goal of this project is to explore the role PBX1 in inhibiting H2O2-induced oxidative damage to HF-MSC and related mechanism from the perspective of DNA damage and repair,which will provides a theoretical basis for hair damage repair and regeneration.