Department of Pediatrics, Northwestern University, Feinberg School of Medicine and Children's Memorial Research Center, Chicago, Illinois, United States of America.
PLoS One. 2012;7(12):e52375. doi: 10.1371/journal.pone.0052375. Epub 2012 Dec 26.
The inability to functionally repair tissues that are lost as a consequence of disease or injury remains a significant challenge for regenerative medicine. The molecular and cellular processes involved in complete restoration of tissue architecture and function are expected to be complex and remain largely unknown. Unlike humans, certain salamanders can completely regenerate injured tissues and lost appendages without scar formation. A parsimonious hypothesis would predict that all of these regenerative activities are regulated, at least in part, by a common set of genes. To test this hypothesis and identify genes that might control conserved regenerative processes, we performed a comprehensive microarray analysis of the early regenerative response in five regeneration-competent tissues from the newt Notophthalmus viridescens. Consistent with this hypothesis, we established a molecular signature for regeneration that consists of common genes or gene family members that exhibit dynamic differential regulation during regeneration in multiple tissue types. These genes include members of the matrix metalloproteinase family and its regulators, extracellular matrix components, genes involved in controlling cytoskeleton dynamics, and a variety of immune response factors. Gene Ontology term enrichment analysis validated and supported their functional activities in conserved regenerative processes. Surprisingly, dendrogram clustering and RadViz classification also revealed that each regenerative tissue had its own unique temporal expression profile, pointing to an inherent tissue-specific regenerative gene program. These new findings demand a reconsideration of how we conceptualize regenerative processes and how we devise new strategies for regenerative medicine.
由于疾病或损伤而丧失的组织的功能修复仍然是再生医学面临的重大挑战。完全恢复组织结构和功能的分子和细胞过程预计将是复杂的，并且在很大程度上仍然未知。与人类不同，某些蝾螈可以在不形成疤痕的情况下完全再生受伤的组织和失去的附属物。一个简约的假设是，所有这些再生活动至少部分受到一组共同基因的调控。为了验证这一假设并确定可能控制保守再生过程的基因，我们对新蝾螈（Notophthalmus viridescens）的五种具有再生能力的组织的早期再生反应进行了全面的微阵列分析。与这一假设一致，我们建立了一个再生的分子特征，其中包括在多种组织类型的再生过程中动态差异调节的常见基因或基因家族成员。这些基因包括基质金属蛋白酶家族及其调节剂、细胞外基质成分、参与控制细胞骨架动力学的基因以及各种免疫反应因子的成员。基因本体论术语富集分析验证并支持了它们在保守再生过程中的功能活性。令人惊讶的是，聚类树状图和 RadViz 分类也表明，每个再生组织都有其独特的时间表达谱，这表明存在内在的组织特异性再生基因程序。这些新发现要求我们重新考虑如何概念化再生过程以及如何为再生医学设计新策略。
