Role of fibroblast Dipeptidyl peptidase 4 (DPP4/CD26) in dermal wound healing, scarring and regeneration

哺乳动物皮肤的创伤导致愈合程序的激活，其特征在于炎症、肉芽组织的重塑和细胞外基质（ECM）的重组，这导致疤痕的形成。另一方面，在发育过程中，即使在炎症存在的情况下，皮肤修复也在无瘢痕形成的情况下进行，直到发生成纤维细胞的谱系定型并且表达DPP4（CD26）的细胞开始构成皮肤中的大部分成纤维细胞。以前的研究和自己的初步数据表明，DPP4对成纤维细胞的调节功能。然而，这种分子在伤口愈合过程中的确切功能仍然未知。通过其二肽酶活性，它可能在创伤修复的特定阶段使细胞因子和生长因子失活，从而影响成纤维细胞和其他周围细胞的行为。自己的实验表明，DPP4在伤口愈合过程中在真皮细胞上表达和调节，当在后期受到抑制时，它会导致毛囊新生增加，这是再生修复的标志。本课题旨在研究DPP4在创伤愈合和创伤诱导毛囊新生过程中的表达、调控和功能。这项研究所产生的知识可能会确定一个目标的调制和改善伤口愈合和减少疤痕

Wounding of mammalian skin results in the activation of a healing program characterized by inflammation, remodeling of granulation tissue and reorganization of the extracellular matrix (ECM) which leads to the formation of a scar. On the other hand, during development, even in the presence of inflammation, skin repair proceeds without scarring until a lineage commitment of fibroblasts occurs and cells expressing DPP4 (CD26) start constituting the majority of fibroblasts in the skin. Previous investigations and own preliminary data suggest a regulatory function for DPP4 on fibroblasts. However, the exact functions of this molecule during wound healing remain unknown. Through its dipeptidase activity it might deactivate cytokines and growth factors at specific stages of wound repair and so influence the behavior of fibroblasts and other surrounding ells. Own experiments show that DPP4 is expressed and regulated on dermal cells during wound healing and when inhibited at late stages it results in increased neogenesis of hair follicles, a hallmark of regenerative repair. The present project aims to determine the pattern of expression, regulation and function of DPP4 during wound healing and wound induced hair follicle neogenesis. The knowledge generated with this investigation might identify targets for a modulation and improvement of wound healing and a reduction of scarring