Feinberg Cardiovascular Research Institute & Division of Nephrology, Northwestern University, Chicago, IL, USA.
Exp Biol Med (Maywood). 2013 May;238(5):461-81. doi: 10.1177/1535370213489441.
Fibrosis, a non-physiological wound healing in multiple organs, is associated with end-stage pathological symptoms of a wide variety of vascular injury and inflammation related diseases. In response to chemical, immunological and physical insults, the body's defense system and matrix synthetic machinery respond to healing the wound and maintain tissue homeostasis. However, uncontrolled wound healing leads to scarring or fibrosis, a pathological condition characterized by excessive synthesis and accumulation of extracellular matrix proteins, loss of tissue homeostasis and organ failure. Understanding the actual cause of pathological wound healing and identification of igniter(s) of fibrogenesis would be helpful to design novel therapeutic approaches to control pathological wound healing and to prevent fibrosis related morbidity and mortality. In this article, we review the significance of a few key cytokines (TGF-β, IFN-γ, IL-10) transcriptional activators (Sp1, Egr-1, Smad3), repressors (Smad7, Fli-1, PPAR-γ, p53, Klotho) and epigenetic modulators (acetyltransferase, methyltransferases, deacetylases, microRNAs) involved in major matrix protein collagen synthesis under pathological stage of wound healing, and the potentiality of these regulators as therapeutic targets for fibrosis treatment. The significance of endothelial to mesenchymal transition (EndMT) and senescence, two newly emerged fields in fibrosis research, has also been discussed.
纤维化是一种发生于多种器官的非生理性创伤愈合，与多种血管损伤和炎症相关疾病的终末期病理症状有关。为了应对化学、免疫和物理刺激，机体的防御系统和基质合成机制会响应创伤并维持组织内稳态。然而，失控的创伤愈合会导致瘢痕或纤维化，这是一种病理状态，其特征是细胞外基质蛋白的过度合成和积累、组织内稳态丧失和器官衰竭。了解病理性创伤愈合的确切原因，并确定纤维化的触发因素，有助于设计新的治疗方法来控制病理性创伤愈合，预防纤维化相关的发病率和死亡率。在本文中，我们综述了在病理性创伤愈合阶段参与主要基质蛋白胶原合成的几种关键细胞因子（TGF-β、IFN-γ、IL-10）转录激活因子（Sp1、Egr-1、Smad3）、转录抑制因子（Smad7、Fli-1、PPAR-γ、p53、Klotho）和表观遗传调节剂（乙酰转移酶、甲基转移酶、去乙酰化酶、microRNAs）的重要性，以及这些调节剂作为纤维化治疗靶点的潜力。内皮细胞向间充质转化（EndMT）和衰老这两个纤维化研究中的新兴领域的意义也进行了讨论。
