Expression of collagen genes in the cones of skin in the Duroc/Yorkshire porcine model of fibroproliferative scarring.
Expression of collagen genes in the cones of skin in the Duroc/Yorkshire porcine model of fibroproliferative scarring.
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DOI：
10.1097/bcr.0b013e3181848141
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
Engrav LH
中科院分区：
文献类型：
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作者：
Zhu KQ;Carrougher GJ;Couture OP;Tuggle CK;Gibran NS;Engrav LH
在过去的几十年里，肥大性疤痕的预防和治疗进展甚微。原因包括缺乏有效的动物模型，将瘢痕解剖成组织学成分的技术不精确，以及测量基因表达的方法有限。这些问题已经通过杜洛克/约克郡愈合模型、激光捕获显微切割和Affyphyspine Porcine GeneChip®得到解决。在这里，我们比较了胶原基因表达的纤维增生性愈合的杜洛克品种的非纤维增生性愈合的约克郡。我们制作了浅和深的背部伤口，在1、2、3、12和20周时进行活检。我们通过激光捕获显微切割对真皮锥进行取样，提取并扩增RNA，并将Affyssin Porcine GeneChips®杂交。我们还获得了约20周后的人增生性瘢痕的样品。将数据标准化，并使用Bioconductor R/maanova软件包用混合线性回归进行统计分析。用于进一步分析的基因也受到四个生物学标准的限制，包括20周深杜洛克表达与人类样本相匹配。11种胶原基因和7种胶原类型在杜洛克深伤口中差异过表达，包括1a 1、1a 2、3a 1、4a 1、4a 2、5a 1、5a 2、5a 3、6a 3（转录变体5）、14 a1和15 a1。COL 7a 1基因在杜洛克犬深创面中差异表达。结果表明，胶原蛋白I，III，IV，V，VI，VII，XIV和XV 1参与纤维增生性瘢痕形成的过程。有了这些线索，我们将尝试构建纤维增生性愈合的调控途径。
During the past decades there has been minimal improvement in prevention and treatment of hypertrophic scarring. Reasons include the lack of a validated animal model, imprecise techniques to dissect scar into the histologic components, and limited methodology for measurement of gene expression. These problems have been addressed with the Duroc/Yorkshire model of healing, laser capture microdissection, and the Affymetrix Porcine GeneChip®. Here we compared collagen gene expression in fibroproliferative healing in the Duroc breed to nonfibroproliferative healing in the Yorkshires. We made shallow and deep dorsal wounds, biopsied at 1, 2, 3, 12, and 20 weeks. We sampled the dermal cones by laser capture microdissection, extracted and amplified the RNA, and hybridized Affymetrix Porcine GeneChips®. We also obtained samples of human hypertrophic scar approximately 20 weeks postinjury. Data were normalized and statistical analysis performed with mixed linear regression using the Bioconductor R/maanova package. Genes for further analysis were also restricted with four biologic criteria, including that the 20-week deep Duroc expression match the human samples. Eleven ollagen genes and seven collagen types were differentially over expressed in deep Duroc wounds including 1a1, 1a2, 3a1, 4a1, 4a2, 5a1, 5a2, 5a3, 6a3 (transcript variant 5), 14a1 and 15a1. COL7a1 gene was differentially under expressed in deep Duroc wounds. The results suggest that collagens I, III, IV, V, VI, VII, XIV, and XV1 are involved in the process of fibroproliferative scarring. With these clues, we will attempt to construct the regulatory pathway(s) of fibroproliferative healing.