Department of Respiratory and Critical Care Medicine, Chengdu Third People's Hospital, Chengdu City, 610031, Sichuan Province, China.
Department of Anatomy, Harbin Medical University, Harbin City, 150081, Heilongjiang Province, China.
Hereditas. 2021 Dec 8;158(1):47. doi: 10.1186/s41065-021-00213-w.
Asthma is a common chronic respiratory disease that influences 300 million people all over the world. However, the pathogenesis of asthma has not been fully elucidated. It has been reported that transforming growth factor-β (TGF-β) can activate myofibroblasts. Moreover, the fibroblast to myofibroblast transformation (FMT) can be triggered by TGF-β, which is a major mediator of subepithelial fibrosis. Secreted modular calcium-binding protein 2 (SMOC2) is a member of cysteine (SPARC) family and is involved in the progression of multiple diseases. However, its role in asthma remains poorly understood. RT-qPCR evaluated the expression of SMOC2. Bromodeoxyuridine assay and wound-healing assay detected the proliferation and migration of lung fibroblasts, respectively. IF staining was performed to assess the expression of α-smooth muscle actin (α-SMA). Western blot analysis detected the levels of proteins. Flow cytometry was utilized for determination of the number of myofibroblasts.
We found the expression of SMOC2 was upregulated by the treatment of TGF-β1 in lung fibroblasts. In addition, SMOC2 promoted the proliferation and migration of lung fibroblasts. More importantly, SMOC2 accelerated FMT of lung fibroblasts. Furthermore, SMOC2 was verified to control the activation of AKT and ERK. Rescue assays showed that the inhibition of AKT and ERK pathway reversed the promoting effect of SMOC2 overexpression on proliferation, migration and FMT in lung fibroblasts.
This work demonstrated that SMOC2 modulated TGF-β1-induced proliferation, migration and FMT in lung fibroblasts and may promote asthma, which potentially provided a novel therapeutic target for the management of asthma.
哮喘是一种常见的慢性呼吸道疾病，影响着全球 3 亿多人。然而，哮喘的发病机制尚未完全阐明。据报道，转化生长因子-β（TGF-β）可以激活肌成纤维细胞。此外，TGF-β可以触发成纤维细胞向肌成纤维细胞转化（FMT），这是上皮下纤维化的主要介导物。分泌模块钙结合蛋白 2（SMOC2）是半胱氨酸（SPARC）家族的成员，参与多种疾病的进展。然而，其在哮喘中的作用仍知之甚少。RT-qPCR 评估了 SMOC2 的表达。溴脱氧尿苷测定和划痕愈合测定分别检测肺成纤维细胞的增殖和迁移。免疫荧光染色评估α-平滑肌肌动蛋白（α-SMA）的表达。Western blot 分析检测蛋白水平。流式细胞术用于测定肌成纤维细胞的数量。
我们发现 TGF-β1 处理可上调肺成纤维细胞中 SMOC2 的表达。此外，SMOC2 促进肺成纤维细胞的增殖和迁移。更重要的是，SMOC2 加速了肺成纤维细胞的 FMT。此外，SMOC2 被证实控制 AKT 和 ERK 的激活。挽救实验表明，AKT 和 ERK 通路的抑制逆转了 SMOC2 过表达对肺成纤维细胞增殖、迁移和 FMT 的促进作用。
这项工作表明，SMOC2 调节 TGF-β1 诱导的肺成纤维细胞增殖、迁移和 FMT，可能促进哮喘，这为哮喘的管理提供了一个新的治疗靶点。
