Interleukin-13 in the pathogenesis of pulmonary artery hypertension

Abstract

Background Interleukin (IL)-13 is a regulatory factor of tissue remodeling and is involved in the pathogenesis of pulmonary artery hypertension (PAH). However, the implications of IL-13 in PAH remains uncertain. This article aims to describe the current knowledge on production and function of IL-13 and its receptors in the mechanisms of PAH. Content The study materials of this article were based on comprehensive literature retrieval of publications of IL-13 in PAH. These study materials were carefully reviewed, analyzed and discussed. Summary IL-13 levels in blood and lung tissue were elevated in both animal models of PAH and patients with PAH in comparison to non-PAH controls. Types I and II IL-13 receptors participate in pulmonary artery remodeling through signal transducer and activator of transcription (STAT)6 or through phosphatidylinositol 3-kinase (PI3K), STAT3 and mitogen activated protein kinase (MAPK) pathways. Oxidant, arginase 2 (Arg2) and hypoxia-inducible factor 1α are involved in the proliferation of pulmonary artery smooth muscle cells. Outlook Types I and II IL-13 receptors play an important role in the IL-13 signaling by STAT6 via Janus kinase kinases, and by PI3K, STAT3 and MAPK pathways, respectively. Alternative pathways, including oxidant, Arg2 and hypoxia-inducible factor 1α might be also involved in the pathological process of PAH development. Investigational therapies by inflammatory suppression or thrombolytic and anticoagulant agents could inhibit intimal hyperplasia of the pulmonary arteries and suppress pulmonary vasculature remodeling. Drug research and development oriented by this hypothesis would confer benefits to the treatment of PAH.

Interleukin-13 promotes cellular senescence through inducing mitochondrial dysfunction in IgG4-related sialadenitis

“…IL-13 activates the intracellular downstream signaling molecules by binding with IL-13Rα1/IL-4Rα heterodimer. 30 We also observed an increased IL-13Rα1 expression in the SMGs of IgG4-RS patients (Fig. 1d, e, f ).…”

Interrelationship and Sequencing of Interleukins4, 13, 31, and 33 – An Integrated Systematic Review: Dermatological and Multidisciplinary Perspectives

“… 36 On the other hand, IL-13 is an important regulatory factor involved in the pathogenesis of pulmonary vascular remodeling and in the development of pulmonary artery hypertension. 37 Concerning the role of IL-13 in inflammatory heart diseases, it was demonstrated that IL-13 deficient mice develop severe myocarditis, having poor prognosis, and that experimental administration of IL-13 could significantly improve heart inflammation and cardiac injury induced by myocarditis. 38 , 39 IL-13 is also associated with progression of valvular heart diseases.…”

Circulating Plasma miRNA and Clinical/Hemodynamic Characteristics Provide Additional Predictive Information About Acute Pulmonary Thromboembolism, Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Hypertension

“…In this way, we have also shown that 11 genes were a direct target of miR-let-7i-5p, which upregulation modulates the proliferation of human PASMCs. Among them, Interleukin13 (IL13) upregulation induces PASMCs in the pulmonary artery through signal transducer and activator of transcription STAT6 or through phosphatidylinositol 3-kinase (PI3K), STAT3 and mitogen activated protein kinase (MAPK) pathways (Yuan, 2019). Oxidant, arginase 2 (ARG2) and hypoxia-inducible factor 1α (HIF1) are also involved in the proliferation of PASMCs (Yuan, 2019).…”

“…Among them, Interleukin13 (IL13) upregulation induces PASMCs in the pulmonary artery through signal transducer and activator of transcription STAT6 or through phosphatidylinositol 3-kinase (PI3K), STAT3 and mitogen activated protein kinase (MAPK) pathways (Yuan, 2019). Oxidant, arginase 2 (ARG2) and hypoxia-inducible factor 1α (HIF1) are also involved in the proliferation of PASMCs (Yuan, 2019). The experimental Schistosomiasisassociated PAH potentially depends on upregulation of IL-13, which can activate TGF-β1 via phospho-STAT6 signaling, or via increased matrix metalloproteinase-inducing muscular hypertrophy and periadventitial fibrosis in pulmonary arteries (Graham et al, 2010).…”

“…Therefore, circulating miRNAs have been widely explored as potential blood-based biomarkers for individual cardiovascular diseases diagnosis. Furthermore, it is also reasonable to assume that identification of molecular pathways and axon guidance enriched by differentially expressed miRNAs target genes and interactions between them provide a molecular basis for the unbalance between hyperproliferative and apoptosis-resistant phenotype particularly in the three principal pulmonary artery cell involved including PAEC, PASMC, and PAAF (Graham et al, 2010;Chen and Jiang, 2018;Yuan, 2019;Santos-Ferreira et al, 2020). Thus, we hypothesize that analyzing different circulating plasma miRNAs in APTE, CTEPH and IPAH, we can describe the early APTE evolution to CTEPH, as well as irreversible fibrocellular narrowing of pulmonary arteries in diseases form, including CTEPH and IPAH.…”