肺纤维化是一种慢性,进步,以肺实质纤维化瘢痕形成为特征的不可逆肺疾病。由于肺泡环境中肌成纤维细胞的异常激活,这种情况涉及细胞外基质(ECM)的过度积累。转化生长因子β(TGF-β)信号传导是纤维发生的关键驱动因素,因为它促进过度的ECM沉积,从而导致瘢痕形成和肺损伤。纤维化中TGF-β信号传导的主要目标是胶原三螺旋重复1(CTHRC1),分泌的糖蛋白,在ECM沉积和伤口修复中起关键作用。TGF-β转录调节CTHRC1对组织损伤的反应,并通过功能活性控制伤口愈合反应。CTHRC1还可以通过调节TGF-β和经典Wnt信号通路在伤口闭合后重建和维持组织稳态中起重要作用。这种双重功能表明CTHRC1调节组织重塑和体内平衡。然而,致病性成纤维细胞中CTHRC1表达失调最近已成为多个器官和组织中纤维化的标志。这篇综述强调了最近的研究,表明CTHRC1可以作为特发性肺纤维化的诊断和预后生物标志物。系统性硬化症,和COVID-19后肺纤维化。值得注意的是,CTHRC1表达对靶向TGF-β途径的抗纤维化药物有反应,例如吡非尼酮和倍西格拉斯特,表明其作为治疗成功的生物标志物的潜力。这些发现表明,CTHRC1可能为诊断和治疗肺纤维化患者提供了新的机会。
Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and
bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.