DNA甲基转移酶1在小鼠皮肤衰老中的作用

目的：探讨DNA甲基转移酶1(DNA methyltransferase 1，DNMT1)在小鼠皮肤衰老中的作用。方法：获取表 皮条件性K14-Cre介导的DNMT1基因敲除鼠(Mut组，n=4)及等月龄同窝正常小鼠(WT组，n=4)，观察皮肤表型的变 化；HE染色检测皮肤组织学变化；Gomori醛复红染色检测两组小鼠真皮弹力纤维数目及形态变化；免疫组织化学染 色法检测5-溴脱氧尿嘧啶核苷(5-bromo-2-deoxyuridine，Brdu)标记的表皮短暂扩充细胞(transit amplifying cells，TAC)含 量；免疫组织荧光染色法检测氯去氧尿苷(chlorodeoxyuridine，CldU)标记的表皮中标记滞留细胞(label-retaining cells， LRC)的含量。结果：与等月龄的同窝WT组相比，Mut组皮肤出现过早衰老的症状；HE染色显示表皮增厚、真皮胶 原纤维减少等老化现象；真皮内弹力纤维断裂变形增多；表皮中TAC的数量明显增多(P<0.05)；LRC的数量明显减少 (P<0.05)。结论：与WT组相比，Mut组出现了皮肤早衰的表型，其机制可能是由于DNMT1敲除后表皮干细胞耗竭所致。

Role of DNA methyltransferase 1 in mouse skin aging

Objective: To explore the role ofDNA methyltransferase 1 (DNMT1) in mouse skin aging. Methods: Epidermal conditional K14 Cre-mediated DNA methyltransferase 1 (DNMT1) knockout mice (Mut group, n=4) and the litt ermate normal mice with the same age (WT group) n=4) were used in this study. HE staining was used to detect the pathological changes of skin; the changes of number in the dermal elastic fi bers were detected by Gomori aldehyde fuchsin staining, the number of 5-bromo-2-deoxyuridine (BrdU)-labeled transit amplifying cells (TAC) in epidermis were detected by immunohistochemical staining; the number of chlorodeoxyuridine (CldU)-labelretaining cells (LRC) in epidermis were detected by immunofl uorescent staining. Results: Compared with the WT group, the skin showed premature aging symptoms in theMut group concomitant with the decreased epidermal thickness as well as the number of dermal collagen fibers, while the increased dermal elastic fiber fracture. Compared with the WT group, the number of TAC in the epidermis was significantly increased (P<0.05), and the number of LRC was significantly decreased (P<0.05) in the Mut group. Conclusion: The phenotype of skin premature aging in epidermal stem cell conditional DNMT1- knockout mice suggests an important role of DNMT1 in skin aging.