miR-29a-3p regulates the epithelial-mesenchymal transition via the SPARC/ERK signaling pathway in human bronchial epithelial cells

Neutrophilic asthma (NA) is a subtype of asthma that responds poorly to corticosteroid treatment. In certain diseases, microRNA (miR)-29a-3p is considered to be a key regulatory molecule for remodeling of the extracellular matrix. However, the effect of miR-29a-3p on airway remodeling is unknown. The present study aimed to investigate the role of miR-29a-3p in NA. A mouse model of NA was established and these animals were compared to normal controls. Both groups of mice were subjected to lung function tests and histopathological analysis. Human bronchial epithelial cells (16HBE) were grown in culture and incubated with secreted protein acidic rich in cysteine (SPARC) and a miR-29a-3p mimic. The expression of miR-29a-3p, SPARC and epithelial-mesenchymal transition (EMT)-related markers were measured using reverse transcription-quantitative PCR and western blotting. Luciferase reporter assay was performed to identify the direct regulatory relationship between miR-29a-3p and SPARC. miR-29a-3p expression was significantly decreased, while SPARC expression was increased in the NA mouse model with a phenotype of EMT. Overexpression of SPARC downregulated the expression of E-cadherin, while it increased the expression of vimentin in 16HBE cells. miR-29a-3p administration reversed the SPARC-induced effects on E-cadherin and vimentin expression. Luciferase assays confirmed that SPARC was the target gene for miR-29a-3p. Furthermore, SPARC overexpression increased the protein expression of phosphorylated (p)-ERK, while transfection with miR-29a-3p mimics significantly inhibited this increase. The data suggested that EMT in the NA mouse model was associated with decreased levels of miR-29a-3p and elevated SPARC. Furthermore, SPARC could induce the formation of EMT in 16HBE cells in vitro and this was directly targeted by miR-29a-3p and mediated by p-ERK, suggesting that miR-29a-3p may participate in the airway remodeling of NA.