Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Rothman Institute of Orthopaedics, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
Biomolecules. 2023 Apr 27;13(5):758. doi: 10.3390/biom13050758.
Excessive scar formation is a hallmark of localized and systemic fibrotic disorders. Despite extensive studies to define valid anti-fibrotic targets and develop effective therapeutics, progressive fibrosis remains a significant medical problem. Regardless of the injury type or location of wounded tissue, excessive production and accumulation of collagen-rich extracellular matrix is the common denominator of all fibrotic disorders. A long-standing dogma was that anti-fibrotic approaches should focus on overall intracellular processes that drive fibrotic scarring. Because of the poor outcomes of these approaches, scientific efforts now focus on regulating the extracellular components of fibrotic tissues. Crucial extracellular players include cellular receptors of matrix components, macromolecules that form the matrix architecture, auxiliary proteins that facilitate the formation of stiff scar tissue, matricellular proteins, and extracellular vesicles that modulate matrix homeostasis. This review summarizes studies targeting the extracellular aspects of fibrotic tissue synthesis, presents the rationale for these studies, and discusses the progress and limitations of current extracellular approaches to limit fibrotic healing.
过度的瘢痕形成是局部和系统性纤维化疾病的一个标志。尽管已经进行了广泛的研究来确定有效的抗纤维化靶点并开发有效的治疗方法，但进行性纤维化仍然是一个重大的医学问题。无论损伤类型或受伤组织的位置如何，富含胶原蛋白的细胞外基质的过度产生和积累是所有纤维化疾病的共同特征。长期以来的一个定论是，抗纤维化方法应该集中在驱动纤维化瘢痕形成的整体细胞内过程上。由于这些方法的效果不佳，现在科学研究的重点是调节纤维化组织的细胞外成分。关键的细胞外参与者包括细胞外基质成分的细胞受体、构成基质结构的大分子、有助于形成坚硬瘢痕组织的辅助蛋白、基质细胞蛋白以及调节基质动态平衡的细胞外囊泡。本综述总结了靶向纤维化组织合成细胞外方面的研究，提出了这些研究的基本原理，并讨论了目前限制纤维化愈合的细胞外方法的进展和局限性。
