Dataset Information

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

ABSTRACT:

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 in vitro 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.

SUBMITTER: Wei R

PROVIDER: S-EPMC9360879 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Wei Ruda R Chen Liting L Li Pengchuan P Lin Chaoyang C Zeng Qingshi Q

American journal of translational research 20220715 7

<h4>Background</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 35958460

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Project description:The chronic phase of pulmonary arterial hypertension (PAH) is associated with vascular remodeling, especially thickening of the smooth muscle layer of large pulmonary arteries and muscularization of small pulmonary vessels, which normally have no associated smooth muscle. Serotonin (5-hydroxytryptamine, 5-HT) has been shown to induce proliferation and hypertrophy of pulmonary artery smooth muscle cells (PASMC), and may be important for in vivo pulmonary vascular remodeling. Here, we show that 5-HT stimulates migration of pulmonary artery PASMC. Treatment with 5-HT for 16h increased migration of PASMC up to four-fold as monitored in a modified Boyden chamber assay. Increased migratory responses were associated with cellular morphological changes and reorganization of the actin cytoskeleton. 5-HT-induced alterations in morphology were previously shown in our laboratory to require cAMP [Lee SL, Fanburg BL. Serotonin produces a configurational change of cultured smooth muscle cells that is associated with elevation of intracellular cAMP. J Cell Phys 1992;150(2):396-405], and the 5-HT4 receptor was pharmacologically determined to be the primary activator of cAMP in bovine PASMC [Becker BN, Gettys TW, Middleton JP, Olsen CL, Albers FJ, Lee SL, et al. 8-Hydroxy-2-(di-n-propylamino)tetralin-responsive 5-hydroxytryptamine4-like receptor expressed in bovine pulmonary artery smooth muscle cells. Mol Pharmacol 1992;42(5):817-25]. We examined the role of the 5-HT4 receptor and cAMP in 5-HT-induced bovine PASMC migration. PASMC express 5-HT4 receptor mRNA, and a 5-HT4 receptor antagonist and a cAMP antagonist completely blocked 5-HT-induced cellular migration. Consistent with our previous report that a cAMP-dependent Cl(-) channel is required for 5-HT-induced morphological changes in PASMC, phenylanthranilic acid, a Cl(-) channel blocker, inhibited actin cytoskeletal reorganization and migration produced by 5-HT. We conclude that 5-HT stimulates PASMC migration and associated cytoskeletal reorganization through the 5-HT4 receptor and cAMP activation of a chloride channel.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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