Gene expression profiling of cutaneous wound healing.
Gene expression profiling of cutaneous wound healing.
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DOI：
10.1186/1479-5876-5-11
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发表时间：
2007-02-21
影响因子：
7.4
通讯作者：
Stroncek DF
中科院分区：
文献类型：
--
作者：
Deonarine K;Panelli MC;Stashower ME;Jin P;Smith K;Slade HB;Norwood C;Wang E;Marincola FM;Stroncek DF
虽然导致伤口修复的事件序列已经在细胞水平上进行了描述，并且在有限程度上在蛋白质水平上进行了描述，但该过程尚未完全阐明。全基因组转录分析工具有望进一步确定这一复杂事件进展的全局图。本研究是安慰剂对照双盲临床试验的一部分，其中基底细胞癌用免疫调节剂-toll样受体7激动剂：咪喹莫特局部治疗。试验安慰剂组的14名基底细胞癌患者接受仅由赋形剂乳膏组成的安慰剂治疗。在治疗前即刻和安慰剂治疗结束时（2、4或8天后）进行皮肤穿刺活检。利用17.5K cDNA微阵列对活检材料进行分析。鉴定了其表达相对于基线（在通过预处理活检诱导伤口之前）改变的四个基因签名。最大的一组主要由炎症基因组成，其表达在整个研究过程中增加。观察到两个额外的特征，其优选包括早期治疗后活检（预治疗活检后2天）中的促炎基因和后期（4至8天）活检中的修复和血管生成基因。第四组也是最小的一组基因在整个研究中被下调。在伤口愈合早期，M1和M2巨噬细胞标志物的表达增加，但后来M2标志物占主导地位。对皮肤伤口的初始反应诱导促炎刺激的强大转录激活，这可能警告宿主防御。随后，在没有感染的情况下，炎症消退，并被血管生成和重塑所取代。理解这种转变可能是由混合巨噬细胞群体向M2巨噬细胞为主的变化驱动的，可能有助于解释连续活检组织微环境中发生的细胞和分子事件。
Although the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events. This study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier – toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days). 17.5K cDNA microarrays were utilized to profile the biopsy material. Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy) were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies) and repair and angiogenesis genes in the later (4 to 8 days) biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated. The initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominately M2 macrophages, may help the interpretation of the cellular and molecular events occurring in the microenvironment of serially biopsied tissues.
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影响因子：
82.9
作者：
He, ZH;Ong, CHP;Bateman, A
通讯作者：
Bateman, A
影响因子：
4.4
作者：
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影响因子：
13.6
作者：
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影响因子：
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作者：
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Wang E
影响因子：
5.3
作者：
Huang, XZ;Griffiths, M;Sheppard, D
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Sheppard, D