Wang Yongping, Zhang Tiantian, Song Hao, Yang Cheng
Frontier Science Center for Synthetic Biology (Ministry of Education), Key Laboratory of Systems Bioengineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, China.
Sci Rep. 2025 Mar 11;15(1):8444. doi: 10.1038/s41598-025-92687-1.
Skin fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) in the dermis, can lead to hypertrophic scars and impaired mobility. The ErbB family of receptor tyrosine kinases, including ErbB1 and ErbB2, plays a crucial role in organ fibrosis, but their specific impact on skin fibrosis is less understood. This study investigated the role of ErbB1 and ErbB2 in skin fibrosis and the therapeutic potential of lapatinib, a dual ErbB1 and ErbB2 tyrosine kinase inhibitor. Using qPCR, cell culture assays, Western blotting, and in vivo models, we found significant upregulation of ErbB1 and ErbB2 in keloid tissues and fibroblasts. Lapatinib treatment resulted in a dose-dependent decrease in ErbB1 and ErbB2 expression, which suppressed the expression of fibroblast activation markers. Our findings suggest that lapatinib may be a promising therapeutic agent for skin fibrosis by targeting ErbB1/ErbB2 and modulating the TGF-β1/Smad2/3/Erk/Akt signalling pathways. These results warrant further clinical investigation into lapatinib for treating skin fibrosis and related conditions.
皮肤纤维化的特征是真皮中细胞外基质（ECM）过度积累，可导致肥厚性瘢痕和活动能力受损。包括ErbB1和ErbB2在内的受体酪氨酸激酶ErbB家族在器官纤维化中起关键作用，但其对皮肤纤维化的具体影响尚不清楚。本研究调查了ErbB1和ErbB2在皮肤纤维化中的作用以及拉帕替尼（一种双重ErbB1和ErbB2酪氨酸激酶抑制剂）的治疗潜力。通过定量聚合酶链反应（qPCR）、细胞培养试验、蛋白质免疫印迹法和体内模型，我们发现瘢痕疙瘩组织和成纤维细胞中ErbB1和ErbB2显著上调。拉帕替尼治疗导致ErbB1和ErbB2表达呈剂量依赖性降低，从而抑制了成纤维细胞活化标志物的表达。我们的研究结果表明，拉帕替尼可能是一种有前景的治疗皮肤纤维化的药物，它通过靶向ErbB1/ErbB2并调节转化生长因子-β1（TGF-β1）/Smad2/3/细胞外信号调节激酶（Erk）/蛋白激酶B（Akt）信号通路发挥作用。这些结果值得对拉帕替尼治疗皮肤纤维化及相关病症进行进一步的临床研究。
