Kim Jihee, Won Chihyeong, Ham Seoyoon, Han Heetak, Shin Sungsik, Jang Jieun, Lee Sanghyeon, Kwon Chaebeen, Cho Sungjoon, Park Hyeonjoo, Lee Dongwon, Lee Won Jai, Lee Taeyoon, Lee Ju Hee
Department of Dermatology, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
School of Electrical and Electronic Engineering, Yonsei University, Seoul 03722, Republic of Korea.
Biomedicines. 2024 Sep 24;12(10):2169. doi: 10.3390/biomedicines12102169.
Keloids are a common fibrotic disease of the skin, with the pathological hallmark of excessive extracellular matrix synthesis due to abnormal fibroblast activity. Since keloids clinically arise in areas of high mechanical tension, the mechanotransductory pathway may be attributed to its pathogenesis. We aimed to establish a preclinical platform to elucidate the underlying mechanism of keloid development and its clinical persistence.
We fabricated a mechanically stretchable polydimethylsiloxane cell culture platform; with its mimicry of the in vivo cyclic stretch of skeletal muscles, cells showed higher proliferation compared with conventional modalities.
In response to mechanical strain, TGF-β and type 1 collagen showed significant increases, suggesting possible TGF-β/Smad pathway activation via mechanical stimulation. Protein candidates selected by proteomic analysis were evaluated, indicating that key molecules involved in cell signaling and oxidative stress were significantly altered. Additionally, the cytoskeletal network of keloid fibroblasts showed increased expression of its components after periodic mechanical stimulation.
Herein, we demonstrated and validated the existing body of knowledge regarding profibrotic mechanotransduction signaling pathways in keloid fibroblasts. Cyclic stretch, as a driving force, could help to decipher the tension-mediated biomechanical processes, leading to the development of optimized therapeutic targets.
瘢痕疙瘩是一种常见的皮肤纤维化疾病，其病理特征是成纤维细胞活动异常导致细胞外基质过度合成。由于瘢痕疙瘩临床上多发生在机械张力较高的部位，机械转导途径可能与其发病机制有关。我们旨在建立一个临床前平台，以阐明瘢痕疙瘩形成及其临床持续存在的潜在机制。
我们制作了一个可机械拉伸的聚二甲基硅氧烷细胞培养平台；该平台模拟骨骼肌的体内周期性拉伸，与传统培养方式相比，细胞增殖能力更强。
在机械应变作用下，转化生长因子-β（TGF-β）和Ⅰ型胶原蛋白显著增加，提示可能通过机械刺激激活TGF-β/Smad信号通路。对蛋白质组学分析筛选出蛋白候选物进行评估，结果表明参与细胞信号传导和氧化应激的关键分子发生了显著变化。此外，周期性机械刺激后，瘢痕疙瘩成纤维细胞的细胞骨架网络成分表达增加。
在此，我们证实并验证了关于瘢痕疙瘩成纤维细胞中促纤维化机械转导信号通路的现有知识体系。周期性拉伸作为一种驱动力，有助于解读张力介导的生物力学过程，从而开发出优化的治疗靶点。
