STOML2 knockdown inhibits inflammation and airway remodeling of PDGF-BB-induced airway smooth-muscle cells by the MAPK pathway.

Abstract

Objective: Asthma is a chronic inflammatory airway disease characterized by airway inflammation and remodeling. Abnormal proliferation and migration of human airway smooth muscle cells (HASMCs), induced by platelet-derived growth factor BB (PDGF-BB), are associated with the occurrence and progression of asthma. In this study, we aim to investigate the expression and molecular mechanisms of stomatin-like protein-2 (STOML2) in airway remodeling in asthma.

Methods: PDGF-BB-stimulated HASMCs were used as the asthma cell model. STOML2 expression levels in the serum of patients with asthma and healthy controls were measured using qRT-PCR. Additionally, qRT-PCR and western blotting were used to measure STOML2, E-cadherin, and N-cadherin expression in HASMCs. Extracellular matrix components were detected by western blot assay. The viability and migration of HASMCs were analyzed using MTT and Transwell assays. Tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 contents were evaluated using the corresponding kits. The key molecules of the p38 mitogen-activated protein kinase (p38 MAPK) pathway (p38 and p38) were determined using western blotting.

Results: Increased STOML2 expression was observed in both patients with asthma and PDGF-BB-treated HASMCs. STOML2 knockdown inhibits STOML2 expression in HASMCs. PDGF-BB induced proliferation, migration, extracellular matrix deposition, inflammatory responses, and p38 MAPK pathway activation in HASMCs. However, the opposite effects were observed following STOML2 knockdown or SB-203580 treatment, respectively. Furthermore, P79350 treatment reversed the effect of STOML2 knockdown.

Conclusions: Our results showed that silencing STOML2 inhibits inflammation and airway remodeling in PDGF-BB-stimulated HASMCs via the p38 MAPK pathway. Thus, STOML2 is a promising therapeutic target for the treatment of asthma.