Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-β/Smad pathway
Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-β/Smad pathway
复制标题
龙血素 B 通过 TGF-β/Smad 通路抑制增生性疤痕中成纤维细胞增殖和细胞外基质沉积
DOI：
10.1111/exd.12665
复制
发表时间：
2015-05-01
影响因子：
3.6
通讯作者：
Hu, Dahai
中科院分区：
文献类型：
--
作者：
Bai, Xiaozhi;He, Ting;Hu, Dahai
据报道，龙树脂的乙醇提取物（RDEE）有益于正常伤口愈合，产生更规则排列的胶原纤维。龙血素B是RDEE的主要成分，被认为对预防和治疗病理性瘢痕有效。为探讨龙血素B对增生性瘢痕（HS）的治疗作用，分离了人HS和正常皮肤（NS）的成纤维细胞。结果表明，龙血素B剂量依赖性地下调HS成纤维细胞中I型胶原（ColI）、III型胶原（ColIII）和-平滑肌肌动蛋白（-SMA）的mRNA和蛋白水平。龙血素B还抑制成纤维细胞增殖活性和细胞周期重分布，但不影响细胞凋亡。在体内兔耳瘢痕模型中，龙血素B显著改善胶原纤维的排列和沉积，降低ColI、ColIII和-SMA的蛋白水平，抑制肌成纤维细胞分化和瘢痕增殖活性。在NS成纤维细胞，龙血素B有效地抑制TGF-1诱导的上调ColI，ColIII和SMA水平，肌成纤维细胞分化和Smad2和Smad3的激活。龙血素B还影响TGF-1刺激的成纤维细胞中主要MMPs和TIMPs的mRNA水平。综上所述，本研究表明龙血素B可通过调节MMPs和TIMPs水平下调纤维化相关分子的表达，抑制瘢痕成纤维细胞增殖，抑制TGF-1诱导的纤维化，可能与TGF-1/Smad2/3通路有关。这些发现表明龙血素B是治疗HS的潜在治疗化合物。
The ethanolic extract of Resina Draconis (RDEE) has been reported beneficial to normal wound healing yielding more regularly arranged collagen fibres. Loureirin B, a major component in RDEE, has been supposed to be effective on the prevention and treatment of pathological scars. To investigate the therapeutic effects of loureirin B on hypertrophic scar (HS), fibroblasts from human HS and normal skin (NS) were isolated. Results showed that loureirin B dose-dependently downregulated both mRNA and protein levels of type I collagen (ColI), type III collagen (ColIII) and -smooth muscle actin (-SMA) in HS fibroblasts. Loureirin B also suppressed fibroblast proliferative activity and redistributed cell cycle, but did not affect cell apoptosis. In vivo rabbit ear scar model, loureirin B significantly improved the arrangement and deposition of collagen fibres, decreased protein levels of ColI, ColIII and -SMA and suppressed myofibroblast differentiation and scar proliferative activity. In NS fibroblasts, loureirin B effectively inhibited TGF-1-induced upregulation of ColI, ColIII and -SMA levels, myofibroblast differentiation and the activation of Smad2 and Smad3. Loureirin B also affected mRNA levels of major MMPs and TIMPs in TGF-1-stimulated fibroblasts. Taken together, this study demonstrates that loureirin B could downregulate the expression of fibrosis-related molecules by regulating MMPs and TIMPs levels, inhibit scar fibroblast proliferation and suppress TGF-1-induced fibrosis, during which TGF-1/Smad2/3 pathway is likely involved. These findings suggest that loureirin B is a potential therapeutic compound for HS treatment.