4E-BP1作为分子变阻器平衡再生愈合与纤维化瘢痕形成
4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.
摘要(中文译文)
高效伤口愈合依赖于紧密协调的蛋白质合成，以支持组织修复所涉及的复杂细胞活动。然而，组织再生过程中调控翻译控制的具体机制仍未被完全阐明。在本研究中，我们鉴定出mTORC1效应分子4E结合蛋白1（4E-BP1）是伤口修复和纤维化重塑的关键调控因子。磷酸化4E-BP1在伤口和纤维化组织中显著增加，提示修复过程中mTORC1/4E-BP1信号轴被动态激活。功能研究表明，4E-BP1基因敲除（模拟4E-BP1完全磷酸化状态）可促进伤口组织中的再上皮化、血管生成和肉芽组织形成，但同时促进肌成纤维细胞活化和过度胶原沉积，并加速博来霉素诱导的皮肤纤维化进展。相反，持续过表达4E-BP1则损害伤口闭合并减弱纤维化反应。此外，在体外实验中，4E-BP1表达直接调控转化生长因子-β1介导的成纤维细胞胶原合成。磷酸化4E-BP1水平及相关转录特征在人类皮肤纤维化瘢痕组织中升高。这些发现表明，4E-BP1作为mTORC1下游效应分子，塑造了修复效率与纤维化重塑之间的平衡。因此，靶向mTORC1/4E-BP1信号轴可能为优化伤口愈合和预防病理性瘢痕提供新的治疗机会。
Abstract
Efficient wound healing relies on tightly coordinated protein synthesis to support the complex cellular activities underlying tissue repair. However, the mechanisms governing translational control during tissue regeneration remain incompletely defined. Here, we identify the mTORC1 effector 4E-binding protein 1 (4E-BP1) as a critical regulator of wound repair and fibrotic remodeling. Phosphorylated 4E-BP1 was markedly increased in wounds and fibrotic tissues, indicating dynamic engagement of the mTORC1/4E-BP1 signaling axis during repair. Functional studies revealed that genetic ablation of 4E-BP1, mimicking fully phosphorylated 4E-BP1, enhanced re-epithelialization, angiogenesis, and granulation tissue formation in wound tissues, yet concurrently promoted myofibroblast activation and excessive collagen deposition, and fibrotic progression in bleomycin-induced skin fibrosis. Conversely, sustained overexpression of 4E-BP1 impaired wound closure and attenuated fibrotic responses. Moreover, in vitro, 4E-BP1 expression directly governed transforming growth factor-β1-mediated fibroblast collagen synthesis. Phosphorylated 4E-BP1 levels and related transcriptional signatures were elevated in human skin fibrotic scar tissues. These findings demonstrate that 4E-BP1 acts as an mTORC1-downstream effector that shapes the balance between reparative efficiency and fibrotic remodeling. Targeting the mTORC1/4E-BP1 signaling axis may therefore offer novel therapeutic opportunities to optimize wound healing and prevent pathological scarring.
如何引用
AMA
Hanyu Dou, Jianzhou Li, Lin Lin, Mengyu Jin, Jingyuan Wang, Hequn Fu, et al. 4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.. Experimental & molecular medicine. 2026; doi:10.1038/s12276-026-01724-0.
APA
Hanyu Dou, Jianzhou Li, Lin Lin, Mengyu Jin, Jingyuan Wang, Hequn Fu, et al (2026). 4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.. Experimental & molecular medicine. https://doi.org/10.1038/s12276-026-01724-0
GB/T 7714
Hanyu Dou, Jianzhou Li, Lin Lin, Mengyu Jin, Jingyuan Wang, Hequn Fu, et al. 4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.[J]. Experimental & molecular medicine, 2026 doi:10.1038/s12276-026-01724-0.
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