In pathological fibrosis, aberrant tissue remodeling with excess extracellular matrix leads to organ dysfunction and eventual morbidity. Diseases of fibrosis create significant global health and economic burdens and are often deadly. Although fibrosis has traditionally been thought of as an irreversible process, a growing body of evidence demonstrates that organ fibrosis can reverse in certain circumstances, especially if an underlying cause of injury can be removed. This body of evidence has uncovered more and more contributors to persistent and nonresolving tissue fibrosis. Here, we review the present knowledge on resolution of organ fibrosis and restoration of near-normal tissue architecture. We emphasize three critical areas of tissue homeostasis that are necessary for fibrosis resolution, namely, the elimination of matrix-producing cells, the clearance of excess matrix, and the regeneration of normal tissue constituents. In so doing, we also highlight how profibrotic pathways interact with one another and where there may be therapeutic opportunities to intervene and remediate pathological persistent fibrosis.

在病理性纤维化中，细胞外基质过多导致异常组织重塑导致器官功能障碍和最终发病。纤维化疾病造成了重大的全球健康和经济负担，而且往往是致命的。尽管纤维化历来被认为是一个不可逆转的过程，但越来越多的证据表明，器官纤维化在某些情况下可以逆转，特别是如果可以消除潜在的损伤原因。这些证据揭示了越来越多的持续性和非消退性组织纤维化的促成因素。在这里，我们回顾了目前关于解决器官纤维化和恢复接近正常组织结构的知识。我们强调纤维化解决所必需的组织稳态的三个关键领域，即消除基质产生细胞，清除多余基质，再生正常组织成分。在此过程中，我们还强调了促纤维化途径如何相互作用，以及可能存在干预和修复病理性持续纤维化的治疗机会。