IL-13 alleviates idiopathic pulmonary hypertension by inhibiting the proliferation of pulmonary artery smooth muscle cells and regulating macrophage infiltration.

Background: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by medial hypertrophy due to pulmonary artery smooth muscle cell (PASMC) hyperplasia. In the present study, we conducted bioinformatic analyses and cellular experiments to assess the involvement of the interleukin-13 (IL-13) in IPAH.

Methods: The differentially expressed genes (DEGs) in IPAH and DEGs in IPAH caused by IL-13 treatment were screened using the GEO database. PPI networks were used to analyze the hub genes. Hypoxia-induced PASMCs were treated with IL-13 for assays. CCK8 and EdU staining were used to observe proliferation of PASMCs, and RT-qPCR was applied to detect the expression of hub genes. The conserved binding sites of microRNAs (miRNAs) in the 3'UTR of hub genes were investigated, and the regulatory relationships of the relevant miRNAs on their targets were verified by RT-qPCR and dual-luciferase assays. The GO and KEGG analyses were performed to study the downstream pathways. The effect of hub genes on immune cell infiltration in IPAH was investigated.

Results: IL-13 altered gene expression in IPAH. IL-13 inhibited the proliferation and the expression of hub genes in PASMCs. The 3'UTR sites between HNRNPA2B1, HNRNPH1, SRSF1, HNRNPU and HNRNPA3 in the hub genes and candidate regulatory miRNAs were well conserved in humans. IL-13-mediated hub genes regulated multiple pathways and influenced immune cell infiltration. Hypoxia-induced PASMCs promoted the M2 polarization of macrophages, whereas IL-13-treated PASMCs skewed the macrophages toward M1 polarization.

Conclusions: IL-13-mediated alterations in hub genes inhibit PASMC proliferation and promote M1 macrophage infiltration in IPAH.