Fibrosis is a common pathological condition associated with abnormal repair after tissue injury. However, the etiology and molecular mechanisms of fibrosis are still not well‐understood. Tumor necrosis factor (TNF)‐like weak inducer of apoptosis (TWEAK) belongs to the TNF superfamily and acts by binding to its receptor, fibroblast growth factor‐inducible 14 (Fn14), thereby activating a variety of intracellular signal transduction pathways in various types of cells. Besides promoting the expression of growth factors, activation of TWEAK/Fn14 signaling after tissue injury can promote the expression of pro‐inflammatory cytokines, which trigger the immune response, thereby exacerbating the injury. Severe or repetitive injury leads to a dysregulated tissue repair process, in which the TWEAK/Fn14 axis promotes the activation and proliferation of myofibroblasts, induces the secretion of the extracellular matrix, and regulates profibrotic mediators to further perpetuate and sustain the fibrotic process. In this review, we summarize the available experimental evidence on the underlying molecular mechanisms by which the TWEAK/Fn14 pathway mediates the development and progression of fibrosis. In addition, we discuss the therapeutic potential of the TWEAK/Fn14 pathway in fibrosis‐associated diseases based on evidence derived from multiple models and cells from injured tissue and fibrotic tissue.

中文翻译：

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TWEAK/Fn14 轴是纤维化的重要参与者

纤维化是与组织损伤后异常修复相关的常见病理状况。然而，纤维化的病因和分子机制仍不清楚。肿瘤坏死因子 (TNF) 样弱凋亡诱导剂 (TWEAK) 属于 TNF 超家族，通过与其受体成纤维细胞生长因子诱导型 14 (Fn14) 结合而起作用，从而激活各种类型的细胞内信号转导通路细胞。除了促进生长因子的表达外，组织损伤后 TWEAK/Fn14 信号的激活可以促进促炎细胞因子的表达，从而触发免疫反应，从而加剧损伤。严重或重复性损伤导致组织修复过程失调，其中 TWEAK/Fn14 轴促进肌成纤维细胞的活化和增殖，诱导细胞外基质的分泌，并调节促纤维化介质以进一步延续和维持纤维化过程。在这篇综述中，我们总结了关于 TWEAK/Fn14 通路介导纤维化发展和进展的潜在分子机制的可用实验证据。此外，我们讨论了 TWEAK/Fn14 通路在纤维化相关疾病中的治疗潜力，这是基于来自多个模型和来自受伤组织和纤维化组织的细胞的证据。我们总结了关于 TWEAK/Fn14 通路介导纤维化发展和进展的潜在分子机制的可用实验证据。此外，我们讨论了 TWEAK/Fn14 通路在纤维化相关疾病中的治疗潜力，这是基于来自多个模型和来自受伤组织和纤维化组织的细胞的证据。我们总结了关于 TWEAK/Fn14 通路介导纤维化发展和进展的潜在分子机制的可用实验证据。此外，我们讨论了 TWEAK/Fn14 通路在纤维化相关疾病中的治疗潜力，这是基于来自多个模型和来自受伤组织和纤维化组织的细胞的证据。