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

成纤维细胞二肽基肽酶 4 (DPP4/CD26) 在真皮伤口愈合、疤痕形成和再生中的作用

• 批准号: 406123790
• 负责人: Dr. Rubén Ferrer, Ph.D.
• 金额: --
• 依托单位: Klinik und Poliklinik für Dermatologie, Venerologie und Allergologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406123790?language=en
• 关键词: Role; fibroblast; Dipeptidyl; peptidase; DPP4

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

哺乳动物皮肤的损伤会导致以炎症、肉芽组织重塑和细胞外基质（ECM）重组为特征的愈合程序的激活，从而导致疤痕的形成。另一方面，在发育过程中，即使存在炎症，皮肤修复过程也不会形成疤痕，直到成纤维细胞谱系承诺发生，表达DPP4 （CD26）的细胞开始构成皮肤中的大部分成纤维细胞。先前的研究和自己的初步数据表明DPP4对成纤维细胞具有调节功能。然而，这种分子在伤口愈合过程中的确切功能尚不清楚。通过其二肽酶活性，它可能在伤口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在伤口愈合期间在真皮细胞上表达和调节，当在后期被抑制时，它会导致毛囊新生增加，这是再生修复的标志。本项目旨在研究DPP4在伤口愈合和伤口诱导毛囊新生过程中的表达、调控和功能。这项调查所产生的知识可能会确定调节和改善伤口愈合和减少疤痕的目标