Wound Regeneration Deficit in Rats Correlates with Low Morphogenetic Potential and Distinct Transcriptome Profile of Epidermis.

Wound Regeneration Deficit in Rats Correlates with Low Morphogenetic Potential and Distinct Transcriptome Profile of Epidermis.
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DOI:
10.1016/j.jid.2017.12.030
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发表时间:
2018-06
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
Plikus MV
Plikus MV
中科院分区:
其他
文献类型:
--
作者:
Guerrero-Juarez CF;Astrowski AA;Murad R;Dang CT;Shatrova VO;Astrowskaja A;Lim CH;Ramos R;Wang X;Liu Y;Lee HL;Pham KT;Hsi TC;Oh JW;Crocker D;Mortazavi A;Ito M;Plikus MV

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在老鼠身上,大的切除伤口显著地再生新的毛囊(HFs)和脂肪,然而人类缺乏这种再生行为。目前,伤口诱导的再生仍然是临床上需要的,但只是部分理解的现象。我们发现,大鼠的大面积切除伤口,在七个品系中不能再生新的HFs。我们比较了小鼠和大鼠在结痂脱落时的伤口转录组,这与小鼠HF再生的开始一致。在这两个物种中,创面真皮和表皮分别共享核心真皮和表皮转录程序,但物种间存在显著差异。与小鼠相比,大鼠表皮表达不同的转录和表观遗传因子、表皮修复、增生和炎症标志物,以及较低水平的WNT信号效应物和调节因子。当在切除伤口表面与触须真皮乳头重新结合时,含有远端触须HF节段的部分厚度皮肤移植物,但不含毛囊间表皮,很容易再生新的触须样HF。总之,我们的研究结果建立了大鼠作为切除伤口愈合的非再生啮齿动物模型,并表明低表皮能力和相关的转录谱可能导致其再生缺陷。未来对大鼠和小鼠的比较可能有助于进一步了解损伤诱导再生的机制及其缺陷的原因。
Large excisional wounds in mice prominently regenerate new hair follicles (HFs) and fat, yet humans are deficient for this regenerative behavior. Currently, wound-induced regeneration remains a clinically desirable, but only partially understood phenomenon. We show that large excisional wounds in rats, across seven strains fail to regenerate new HFs. We compared wound transcriptomes between mice and rats at the time of scab detachment, which coincides with the onset of HF regeneration in mice. In both species, wound dermis and epidermis share core dermal and epidermal transcriptional programs respectively, yet prominent inter-species differences exist. Compared to mice, rat epidermis expresses distinct transcriptional and epigenetic factors, markers of epidermal repair, hyperplasia, and inflammation, and lower levels of WNT signaling effectors and regulators. When recombined on the surface of excisional wounds with vibrissa dermal papillae, partial-thickness skin grafts containing distal pelage HF segments, but not interfollicular epidermis, readily regenerated new vibrissa-like HFs. Together, our findings establish rats as a non-regenerating rodent model for excisional wound healing and suggest that low epidermal competence and associated transcriptional profile may contribute to its regenerative deficiency. Future comparison between rat and mouse may lend further insight into the mechanism of wounding-induced regeneration and causes for its deficit.
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