Morales Krista, Rowehl Leahana, Smith Jason, Cole Rich, Liu Fang, Beyer Barb, Herron Bruce J
Wadsworth Center , NYS Department of Health, Albany, New York.
Forensic Biology, State University of New York at Albany , Albany, New York.
Adv Wound Care (New Rochelle). 2014 Sep 1;3(9):563-572. doi: 10.1089/wound.2013.0501.
MRL/MpJ mice are known for enhanced healing, but mechanistic details or how specific aspects of wounding (., angiogenesis) contribute to healing are unknown. While previous studies investigated the systemic effects of immunity in MRL/MpJ healing, few have focused on tissue-intrinsic effects. skin biopsies from MRL/MpJ and C57BL/6J mice were cultured in conditions that favor endothelial cell growth to compare their angiogenic potential. We localized enhanced angiogenesis quantitative trait loci (QTL) in an F2 intercross. We then performed an expression analysis in cultured skin biopsies from MRL/MpJ and C57BL/6J mice to determine the pathways that are associated with the capacity for differential growth. MRL/MpJ biopsies have a two- to threefold greater growth potential than C57BL/6J mice, supporting the hypothesis that angiogenesis may contribute to enhanced healing in MRL/MpJ skin. We mapped two QTLs that are unique from previously mapped MRL/MpJ wound healing QTLs and detected interactions between wound healing QTLs and loci in this cross. Additionally, we found that pathways previously implicated in MRL/MpJ healing are also enriched in skin biopsies. We have developed a novel approach to determine how specific aspects of tissue development contribute to wound healing that will ultimately lead to the discovery of unidentified genes that contribute to enhanced healing. We have shown that, consistent with previous studies following wound closure in MRL/MpJ mice, vessel growth during healing is also influenced by genetic background. Our ongoing work will identify the genetic factors that should be useful biomarkers or as therapeutic targets for enhanced wound healing.
MRL/MpJ小鼠以其增强的愈合能力而闻名，但关于其机制细节或伤口的特定方面（如血管生成）如何促进愈合尚不清楚。虽然先前的研究调查了免疫在MRL/MpJ愈合中的全身作用，但很少有研究关注组织内在效应。将MRL/MpJ和C57BL/6J小鼠的皮肤活检组织在有利于内皮细胞生长的条件下培养，以比较它们的血管生成潜力。我们在F2杂交中定位了增强的血管生成数量性状基因座（QTL）。然后，我们对MRL/MpJ和C57BL/6J小鼠培养的皮肤活检组织进行了表达分析，以确定与差异生长能力相关的途径。MRL/MpJ活检组织的生长潜力比C57BL/6J小鼠大两到三倍，支持了血管生成可能有助于MRL/MpJ皮肤增强愈合的假设。我们绘制了两个与先前绘制的MRL/MpJ伤口愈合QTL不同的QTL，并在该杂交中检测到伤口愈合QTL与基因座之间的相互作用。此外，我们发现先前与MRL/MpJ愈合相关的途径在皮肤活检组织中也很丰富。我们开发了一种新方法来确定组织发育的特定方面如何促进伤口愈合，这最终将导致发现有助于增强愈合的未知基因。我们已经表明，与先前对MRL/MpJ小鼠伤口闭合后的研究一致，愈合过程中的血管生长也受遗传背景的影响。我们正在进行的工作将确定那些可作为增强伤口愈合的有用生物标志物或治疗靶点的遗传因素。
