Departments of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia.
Hudson Institute of Medical Research, Melbourne, Victoria, Australia.
Exp Dermatol. 2021 Mar;30(3):402-408. doi: 10.1111/exd.14223. Epub 2020 Nov 16.
Keloids are benign tumours caused by abnormal wound healing driven by increased expression of cytokines, including activin A. This study compared effects of activins on normal and keloid-derived human dermal fibroblasts and investigated a novel treatment for keloids using follistatin. Normal skin and keloid tissue samples from 11 patients were used to develop primary fibroblast cultures, which were compared in terms of their histology and relevant gene (qRT-PCR and RNAseq) and protein (ELISA) expression. Activin A (INHBA) and connective tissue growth factor (CTGF) gene expression were significantly upregulated in keloid fibroblasts, as was activin A protein expression in cell lysates and culture medium. Activator protein 1 inhibitor (SR11302) significantly decreased INHBA and CTGF expression in keloid fibroblasts and a single treatment of follistatin over 5 days significantly inhibited activin and various matrix-related genes in keloid fibroblasts when compared to controls. Follistatin, by binding activin A, suppressed CTGF expression suggesting a novel therapeutic role in managing keloids and perhaps other fibrotic diseases.
瘢痕疙瘩是由细胞因子表达增加引起的异常伤口愈合导致的良性肿瘤，包括激活素 A。本研究比较了激活素对正常和瘢痕疙瘩来源的人真皮成纤维细胞的影响，并使用卵泡抑素研究了瘢痕疙瘩的一种新的治疗方法。从 11 名患者中获取正常皮肤和瘢痕疙瘩组织样本以开发原代成纤维细胞培养物，并从组织学和相关基因（qRT-PCR 和 RNAseq）和蛋白（ELISA）表达方面进行比较。瘢痕疙瘩成纤维细胞中激活素 A（INHBA）和结缔组织生长因子（CTGF）基因表达显著上调，细胞裂解物和培养基中的激活素 A 蛋白表达也显著上调。激活素蛋白 1 抑制剂（SR11302）可显著降低瘢痕疙瘩成纤维细胞中 INHBA 和 CTGF 的表达，与对照组相比，5 天内单次使用卵泡抑素可显著抑制瘢痕疙瘩成纤维细胞中激活素和各种基质相关基因的表达。卵泡抑素通过与激活素 A 结合抑制 CTGF 的表达，这表明其在管理瘢痕疙瘩和其他纤维化疾病方面具有新的治疗作用。
