Interferon regulatory factor 6 is required for proper wound healing in vivo.

Interferon regulatory factor 6 is required for proper wound healing in vivo.
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DOI:
10.1002/dvdy.134
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发表时间:
2020-04
影响因子:
2.5
通讯作者:
Dunnwald, Martine
Dunnwald, Martine
中科院分区:
生物学3区
文献类型:
--
作者:
Rhea, Lindsey;Canady, Franklin J.;Le, Marc;Reeb, Tanner;Canady, John W.;Kacmarynski, Deborah S. F.;Avvari, Rishika;Biggs, Leah C.;Dunnwald, Martine

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货车德沃德综合征(VWS)是最常见的综合征性口面裂,主要由干扰素调节因子6(IRF 6)突变引起。我们以前报道过,与非综合征性唇腭裂(非综合征性唇腭裂-NSCLP)患者相比,VWS患者在唇腭裂修复后伤口愈合并发症的风险增加。在体外,IRF 6的缺乏导致受损的角质形成细胞迁移和胚胎伤口愈合。然而,目前还没有关于成年动物和VWS中IRF 6水平降低的细胞中组织修复的数据。在受伤后4天和7天分析Irf 6 +/-和野生型动物的切除伤口。尽管所有伤口在7天后都再上皮化,但Irf 6 +/-组修复伤口的表皮和伤口体积较大。这些数据得到了新形成表皮中角质形成细胞增殖增加和细胞因子水平增加的较不成熟肉芽组织的支持。这种效应不是细胞自主的,因为体外Irf 6 +/−新生角质形成细胞在划痕伤口闭合或增殖方面没有表现出缺陷。来自VWS个体的角质形成细胞也与来自NSCLP个体的角质形成细胞类似地迁移。这些数据支持IRF 6通过调节角质形成细胞增殖、肉芽组织成熟和细胞因子水平在伤口愈合中的作用。
Van der Woude syndrome (VWS) is the most common form of syndromic orofacial cleft caused predominantly by mutations in Interferon Regulatory Factor 6 (IRF6). We previously reported that individuals with VWS have increased risk of wound healing complications following cleft repair compared with individuals with nonsyndromic orofacial clefts (nonsyndromic cleft lip and palate—NSCLP). In vitro, absence of IRF6 leads to impaired keratinocyte migration and embryonic wound healing. However, there is currently no data on tissue repair in adult animals and cells with reduced levels of IRF6 like in VWS. Excisional wounds of Irf6+/− and wild-type animals were analyzed 4 and 7 days post-wounding. Although all wounds were reepithelialized after 7 days, the epidermal and wound volume of repaired wounds was larger in Irf6+/−. These data were supported by increased keratinocyte proliferation in the neoformed epidermis and a less mature granulation tissue with increased cytokine levels. This effect was not cell autonomous, as Irf6+/− neonatal keratinocytes in vitro did not exhibit defects in scratch wound closure or proliferation. Keratinocytes from individuals with VWS also migrated similarly to keratinocytes from NSCLP individuals. These data support a role for IRF6 in wound healing by regulating keratinocyte proliferation, granulation tissue maturation, and cytokine levels.
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发表时间: 2012-01
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