CXCR7 promotes the migration of fibroblasts derived from patients with acquired laryngotracheal stenosis by NF-κB signaling.

BACKGROUND

Laryngotracheal stenosis (LTS) is a life-threatening disease that commonly results in airway obstruction in children. Traditional treatments such as laryngotracheal reconstruction and balloon dilation all have the risk of laryngotracheal restenosis. It is of great importance to spare patients the morbidity of LTS and risks of restenosis associated with these treatments. Laboratory and clinical trials have focused on fibrosis, the crucial pathological process of LTS. This study was undertaken to investigate the function of CXC chemokine receptor-7 () in the fibroblasts derived from LTS.

METHODS

RNA sequencing was performed on acquired human LTS and normal trachea tissues to analyze differentially expressed genes. Fibroblasts from LTS and normal trachea tissues were isolated and cultured. knockdown was performed using specific small interfering RNAs (siRNAs) and activated by CXCR7 agonist VUF11207. The assessment of cell proliferation and migration was conducted using EdU proliferation, wound healing, and transwell assays. The assessment of cell proliferation and migration was conducted using EdU proliferation, wound healing, and transwell assays. The expressions of , and NF-κB signaling pathway were analyzed by quantitative polymerase chain reaction (qPCR), western blotting, immunohistochemistry, and immunofluorescence.

RESULTS

RNA sequencing showed that was among the most differentially expressed genes. LTS had an increased CXCR7 expression but decreased E-cadherin expression . CXCR7 agonist stimulated the migration of LTS derived fibroblasts significantly , with no significant influence on the cell proliferation and apoptosis. CXCR7 agonist inhibited the expression of by activating the NF-κB signaling pathway. The effects of on cell migration and expression were blocked by siRNA.

CONCLUSIONS

LTS had an increased expression but decreased expression. activation inhibited expression by NF-κB signaling pathway and thereby promoted the migration of LTS derived fibroblasts.