Cai Yumei, Zhu Shize, Yang Weiqun, Pan Mingmeng, Wang Chaoyang, Wu Wenyi
1 Department of Pathology, Quanzhou Medical College, Quanzhou, China.
2 Department of Plastic Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Tumour Biol. 2017 Jun;39(6):1010428317707423. doi: 10.1177/1010428317707423.
Keloid is a disorder of fibroproliferative diseases that occurs in wounds, characterized by an exaggerated response to injury. The key factor responsible for the disease process has not been identified. This study sought to elucidate the role of β-catenin in the regulation of keloid phenotypes and signaling. Expression of β-catenin in keloid and normal non-keloid samples was measured by real-time polymerase chain reaction. Knockdown of β-catenin was achieved by delivering small interfering RNA to target β-catenin. Cell proliferation, cell cycle progression, and apoptosis of keloid cells were measured by functional assays in vitro. The proteins related to keloid fibrosis were measured by Western blotting. β-catenin expression was significantly upregulated in keloid tissue samples compared with the normal non-keloid age-adjusted skin sample counterparts. Functionally, targeting β-catenin with lipofection-delivered small interfering RNA oligonucleotide inhibited the proliferation and cell cycle arrest in G0/G1 phase and increased apoptosis of fibroblast cells, accompanied by downregulation of Wnt2 and cyclin D1 as well as the phosphorylation level of glycogen synthase kinase 3 beta in the keloid fibrosis. Our study supports a crucial role of β-catenin in the regulation of fibroproliferation and extracellular matrix deposition. Targeting β-catenin using small interfering RNA oligonucleotide may be a promising approach for preventing excessive fibroproliferative development after wound healing and may lead to the development of novel strategies for restoring keloid diseases.
瘢痕疙瘩是一种发生于伤口的纤维增生性疾病，其特征为对损伤的过度反应。导致该疾病进程的关键因素尚未明确。本研究旨在阐明β-连环蛋白在瘢痕疙瘩表型和信号调控中的作用。通过实时聚合酶链反应测定瘢痕疙瘩和正常非瘢痕疙瘩样本中β-连环蛋白的表达。通过递送小干扰RNA靶向β-连环蛋白来实现其敲低。通过体外功能测定来检测瘢痕疙瘩细胞的细胞增殖、细胞周期进程和凋亡情况。通过蛋白质印迹法测定与瘢痕疙瘩纤维化相关的蛋白质。与年龄匹配的正常非瘢痕疙瘩皮肤样本相比，瘢痕疙瘩组织样本中β-连环蛋白的表达显著上调。在功能上，用脂质体递送的小干扰RNA寡核苷酸靶向β-连环蛋白可抑制成纤维细胞的增殖并使其细胞周期停滞于G0/G1期，增加细胞凋亡，同时伴有瘢痕疙瘩纤维化中Wnt2、细胞周期蛋白D1的下调以及糖原合酶激酶3β的磷酸化水平降低。我们的研究支持β-连环蛋白在纤维增生和细胞外基质沉积调控中起关键作用。使用小干扰RNA寡核苷酸靶向β-连环蛋白可能是预防伤口愈合后过度纤维增生性发展的一种有前景的方法，并可能导致开发出恢复瘢痕疙瘩疾病的新策略。
