Pang Xinfeng, Qiao Jing
Medical Laboratory Center, Jiaozuo Women's and Children's Hospital, Jiaozuo 454000, Henan, P.R. China.
Pediatric Respiratory Medicine, Jiaozuo Women's and Children's Hospital, Jiaozuo 454000, Henan, P.R. China.
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20193899.
Childhood asthma is one of the most common chronic childhood diseases. Platelet-derived growth factor BB (PDGF-BB) induced airway smooth muscle cell (ASMC) proliferation and migration are involved in the pathogenesis of asthma. Galectin-1 (Gal-1) is a glycan-binding protein that has been found to be involved in the progression of asthma. However, the mechanism remains unclear. In the current study, we aimed to evaluate the role of Gal-1 in regulating the phenotype switching of ASMCs, which is an important mechanism in the pathogenesis of asthma. Our results showed that Gal-1 was markedly down-regulated in the samples from asthma patients. In vitro study also proved that Gal-1 expression was decreased in PDGF-BB-stimulated ASMCs. In addition, Gal-1 overexpression significantly inhibited PDGF-BB-induced ASMCs proliferation and migration, while Gal-1 knockdown exhibits opposite effects of Gal-1 overexpression. The PDGF-BB-caused reductions in expressions of α-smooth muscle actin (α-SMA), specific muscle myosin heavy chain (SM-MHC), and calponin were elevated by Gal-1 overexpression, but were deteriorated by Gal-1 knockdown in ASMCs. Furthermore, overexpression of Gal-1 inhibited PDGF-BB-stimulated PI3K/Akt activation in ASMCs. Notably, treatment with IGF-1, an activator of PI3K, reversed the effects of Gal-1 on ASMCs proliferation, migration, and phenotype switching. In conclusion, these findings showed that Gal-1 exerted inhibitory effects on PDGF-BB-stimulated proliferation, migration, and phenotype switching of ASMCs via inhibiting the PI3K/Akt signaling pathway. Thus, Gal-1 might be a promising target for the treatment of asthma.
儿童哮喘是最常见的儿童慢性疾病之一。血小板衍生生长因子BB（PDGF-BB）诱导的气道平滑肌细胞（ASMC）增殖和迁移参与哮喘的发病机制。半乳糖凝集素-1（Gal-1）是一种糖结合蛋白，已发现其参与哮喘的进展。然而，其机制仍不清楚。在本研究中，我们旨在评估Gal-1在调节ASMC表型转换中的作用，这是哮喘发病机制中的一个重要机制。我们的结果表明，哮喘患者样本中Gal-1明显下调。体外研究也证明，在PDGF-BB刺激的ASMC中Gal-1表达降低。此外，Gal-1过表达显著抑制PDGF-BB诱导的ASMC增殖和迁移，而Gal-1基因敲低则表现出与Gal-1过表达相反的作用。Gal-1过表达使PDGF-BB导致的α-平滑肌肌动蛋白（α-SMA）、特异性肌球蛋白重链（SM-MHC）和钙调蛋白表达降低得到升高，但在ASMC中Gal-1基因敲低使其恶化。此外，Gal-1过表达抑制PDGF-BB刺激的ASMC中PI3K/Akt激活。值得注意的是，用PI3K激活剂IGF-1处理可逆转Gal-1对ASMC增殖、迁移和表型转换的影响。总之，这些发现表明Gal-1通过抑制PI3K/Akt信号通路对PDGF-BB刺激的ASMC增殖、迁移和表型转换发挥抑制作用。因此，Gal-1可能是治疗哮喘的一个有前景的靶点。
