Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.
Alteration of skin wound healing in keratinocyte-specific mediator complex subunit 1 null mice.
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DOI：
10.1371/journal.pone.0102271
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Itami S
中科院分区：
文献类型：
--
作者：
Noguchi F;Nakajima T;Inui S;Reddy JK;Itami S
MED 1（Mediator complex subunit 1）是多种转录因子的共激活因子，在多种转录途径中发挥作用。我们已经建立了发生表皮增生的角质形成细胞特异性MED 1 null小鼠（Med 1 epi −/−）。在此，为了研究MED 1在皮肤伤口愈合中的功能，在Med 1 epi −/−和年龄匹配的野生型小鼠中产生全层皮肤伤口，并分析愈合过程。与年龄匹配的野生型小鼠相比，8周龄Med 1 epi −/−小鼠的肉眼可见伤口闭合和上皮再形成速度加快。在8周龄的Med 1 epi −/−小鼠中观察到迁移上皮舌的长度增加和受伤表皮处Ki 67阳性细胞的数量增加，而伤口收缩和肉芽组织中α-SMA阳性肌成纤维细胞的面积不受影响。与野生型体外角质形成细胞相比，Med 1 epi −/−角质形成细胞的迁移增强。免疫印迹显示，在Med 1 epi −/−角质形成细胞中卵泡抑素的表达显著降低。此外，在体外用激活素A处理Med 1 epi −/−角质形成细胞之前和之后，丝裂原活化蛋白激酶途径增强。细胞周期分析显示，与野生型角质形成细胞相比，激活素A处理Med 1 epi −/−角质形成细胞后S期细胞的比例增加。这些发现表明，激活素-卵泡抑素系统参与了8周龄Med 1 epi −/−小鼠皮肤伤口愈合的加速。另一方面，与年龄匹配的野生型小鼠相比，6个月大的Med 1 epi −/−小鼠的皮肤伤口愈合显著延迟，受伤表皮的Ki 67阳性细胞数量减少，毛囊中的BrdU阳性标记保留细胞数量减少。这些结果与我们之前的观察一致，即老年Med 1 epi −/−小鼠的毛囊隆起干细胞减少，表明6个月大的Med 1 epi −/−小鼠受伤后毛囊干细胞对表皮再生的贡献减少。这项研究揭示了MED 1在角质形成细胞中的新功能，并提出了一种可能的皮肤伤口愈合和衰老的新治疗方法。
MED1 (Mediator complex subunit 1) is a co-activator of various transcription factors that function in multiple transcriptional pathways. We have already established keratinocyte-specific MED1 null mice (Med1epi−/−) that develop epidermal hyperplasia. Herein, to investigate the function(s) of MED1 in skin wound healing, full-thickness skin wounds were generated in Med1epi−/− and age-matched wild-type mice and the healing process was analyzed. Macroscopic wound closure and the re-epithelialization rate were accelerated in 8-week-old Med1epi−/− mice compared with age-matched wild-type mice. Increased lengths of migrating epithelial tongues and numbers of Ki67-positive cells at the wounded epidermis were observed in 8-week-old Med1epi−/− mice, whereas wound contraction and the area of α-SMA-positive myofibroblasts in the granulation tissue were unaffected. Migration was enhanced in Med1epi−/− keratinocytes compared with wild-type keratinocytes in vitro. Immunoblotting revealed that the expression of follistatin was significantly decreased in Med1epi−/− keratinocytes. Moreover, the mitogen-activated protein kinase pathway was enhanced before and after treatment of Med1epi−/− keratinocytes with activin A in vitro. Cell-cycle analysis showed an increased ratio of S phase cells after activin A treatment of Med1epi−/− keratinocytes compared with wild-type keratinocytes. These findings indicate that the activin-follistatin system is involved in this acceleration of skin wound healing in 8-week-old Med1epi−/− mice. On the other hand, skin wound healing in 6-month-old Med1epi−/− mice was significantly delayed with decreased numbers of Ki67-positive cells at the wounded epidermis as well as BrdU-positive label retaining cells in hair follicles compared with age-matched wild-type mice. These results agree with our previous observation that hair follicle bulge stem cells are reduced in older Med1epi−/− mice, indicating a decreased contribution of hair follicle stem cells to epidermal regeneration after wounding in 6-month-old Med1epi−/− mice. This study sheds light on the novel function of MED1 in keratinocytes and suggests a possible new therapeutic approach for skin wound healing and aging.
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影响因子：
23.9
作者：
Brownell, Isaac;Guevara, Elizabeth;Bai, C. Brian;Loomis, Cynthia A.;Joyner, Alexandra L.
通讯作者：
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作者：
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通讯作者：
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影响因子：
64.8
作者：
Ge, K;Guermah, M;Roeder, RG
通讯作者：
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