Institute of Pathology, RWTH University of Aachen, Germany.
Division of Nephrology, RWTH University of Aachen, Germany.
Mol Aspects Med. 2018 Aug;62:44-62. doi: 10.1016/j.mam.2017.11.008. Epub 2017 Nov 22.
Fibrosis is part of a tissue repair response to injury, defined as increased deposition of extracellular matrix. In some instances, fibrosis is beneficial; however, in the majority of diseases fibrosis is detrimental. Virtually all chronic progressive diseases are associated with fibrosis, representing a huge number of patients worldwide. Fibrosis occurs in all organs and tissues, becomes irreversible with time and further drives loss of tissue function. Various cells types initiate and perpetuate pathological fibrosis by paracrine activation of the principal cellular executors of fibrosis, i.e. stromal mesenchymal cells like fibroblasts, pericytes and myofibroblasts. Multiple pathways are involved in fibrosis, platelet-derived growth factor (PDGF)-signaling being one of the central mediators. Stromal mesenchymal cells express both PDGF receptors (PDGFR) α and β, activation of which drives proliferation, migration and production of extracellular matrix, i.e. the principal processes of fibrosis. Here, we review the role of PDGF signaling in organ fibrosis, with particular focus on the more recently described ligands PDGF-C and -D. We discuss the potential challenges, opportunities and open questions in using PDGF as a potential target for anti-fibrotic therapies.
纤维化是组织对损伤的修复反应的一部分，定义为细胞外基质的过度沉积。在某些情况下，纤维化是有益的；然而，在大多数疾病中，纤维化是有害的。几乎所有的慢性进行性疾病都与纤维化有关，代表了全球大量的患者。纤维化发生在所有器官和组织中，随着时间的推移变得不可逆转，并进一步导致组织功能丧失。各种细胞类型通过旁分泌激活纤维化的主要细胞执行者，即成纤维细胞、周细胞和肌成纤维细胞，启动并延续病理性纤维化。多种途径参与纤维化，血小板衍生生长因子 (PDGF) 信号转导是其中的一个中心介质。基质间充质细胞表达 PDGF 受体 (PDGFR)α 和β，其激活可促进增殖、迁移和细胞外基质的产生，即纤维化的主要过程。在这里，我们综述了 PDGF 信号在器官纤维化中的作用，特别关注最近描述的配体 PDGF-C 和 -D。我们讨论了将 PDGF 用作抗纤维化治疗的潜在靶点的潜在挑战、机遇和开放性问题。
