Grafanaki Katerina, Maniatis Alexandros, Sotiropoulou Vasilina, Pasmatzi Efstathia, Tzouvelekis Argyris
Department of Dermatology-Venereology, School of Medicine, University of Patras, 26504 Patras, Greece.
Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece.
Int J Mol Sci. 2025 Aug 29;26(17):8394. doi: 10.3390/ijms26178394.
Fibrotic diseases of the skin and lung, such as systemic sclerosis, hypertrophic scars, keloids, and pulmonary fibrosis, share core molecular mechanisms despite their distinct anatomical settings. Central to their pathogenesis are persistent fibroblast activation, immune dysregulation, ECM remodeling, and failure of resolution pathways, all modulated by an ever-changing environment and epigenetic regulation. Increasing evidence reveals that chronic injury from air pollution, ultraviolet radiation, climate stressors, and occupational hazards accelerates fibroinflammatory remodeling across these barrier organs. Moreover, shared signaling networks, including TGF-β, IL-4/IL-13, Wnt/β-catenin, and epigenetic regulators like miR-21 and miR-29, suggest convergent fibrotic programs may be subject to cross-organ therapeutic targeting. This review integrates recent insights into the exposome's role in driving fibrosis, highlights novel RNA- and epigenetic-based interventions, and evaluates the repurposing of antifibrotic agents approved for pulmonary disease within dermatologic contexts. We emphasize the emerging concept of fibrosis-aware precision medicine and propose a unifying framework to guide integrated therapeutic strategies. In the face of global climate change and rising environmental insults, a cross-organ perspective on fibrosis offers a timely and translationally relevant approach to addressing this growing burden on human health.
皮肤和肺部的纤维化疾病，如系统性硬化症、增生性瘢痕、瘢痕疙瘩和肺纤维化，尽管其解剖学背景不同，但具有共同的核心分子机制。其发病机制的核心是成纤维细胞持续活化、免疫失调、细胞外基质重塑以及修复途径的失效，所有这些都受到不断变化的环境和表观遗传调控的影响。越来越多的证据表明，空气污染、紫外线辐射、气候压力源和职业危害造成的慢性损伤会加速这些屏障器官的纤维炎症重塑。此外，包括转化生长因子-β（TGF-β）、白细胞介素-4/白细胞介素-13（IL-4/IL-13）、Wnt/β-连环蛋白以及微小RNA-21（miR-21）和微小RNA-29（miR-29）等表观遗传调节因子在内的共享信号网络表明，趋同的纤维化程序可能适用于跨器官治疗靶点。本综述整合了关于暴露组在驱动纤维化中作用的最新见解，强调了基于RNA和表观遗传学的新型干预措施，并评估了在皮肤病学背景下批准用于肺部疾病的抗纤维化药物的重新利用。我们强调了纤维化精准医学这一新兴概念，并提出了一个统一框架来指导综合治疗策略。面对全球气候变化和日益严重的环境损害，对纤维化的跨器官视角为应对这一日益加重的人类健康负担提供了一种及时且具有转化相关性的方法。
