IL‐13 signaling through IL‐13 receptor α2 mediates airway epithelial wound repair

Yang, Shuai; Allahverdian, Sima; Saunders, Angela D. R.; Liu, Emily; Dorscheid, Delbert R.

doi:10.1096/fj.201801285r

Cited by 21 publications

(21 citation statements)

References 54 publications

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“…2 a). This is based on loss of function approach suggesting that in the absence of IL-4Rα/IL-13Rα1 heterodimer (receptor subunit for IL-4 and IL-13), IL-13 can only exert its effects on cognitive function by signaling via the only other available receptor subunit, which is IL-13Rα2 30 , 31 .…”

Section: Discussionmentioning

confidence: 99%

IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory

Brombacher

Berkiks

Pillay

et al. 2020

Sci Rep

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Like pro-inflammatory cytokines, the role of anti-inflammatory cytokines in both learning and memory has been investigated, revealing beneficial effects for both interleukin-4 and interleukin-13 via the common interleukin-4 receptor alpha chain complex. In this study, using the Morris water maze spatial task for cognition, we compared interleukin-4 receptor alpha- deficient mice and their ligands interleukin-4/ interleukin-13 double deficient mice, on a Balb/c background. We demonstrate that while interleukin-4/ interleukin-13 double deficient mice are significantly impaired in both learning and reference memory, interleukin-4 receptor alpha-deficiency impairs only reference memory, compared to the wild-type control mice. In order to better understand how interleukin-4 receptor alpha- deficient mice are able to learn but not remember, we investigated the BDNF/TrkB- and the ARC-signaling pathways. We show that interleukin-4 receptor alpha-deficiency disrupts activation of BDNF/TrkB- and ARC-signaling pathways during reference memory, while the pathway for spatial learning is spared.

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Section: Discussionmentioning

confidence: 99%

IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory

Brombacher

Berkiks

Pillay

et al. 2020

Sci Rep

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“…Asthma is a complicated airway inflammatory disease characterized by airway remodelling resulting from epithelial damage, glandular hyperplasia and subepithelial fibrosis . Current epidemiological results show that asthma has affected approximately 300 million individuals worldwide .…”

Section: Introductionmentioning

confidence: 99%

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Liu

Zhou

et al. 2020

J Cellular Molecular Medi

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Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF‐β1. RACK1 is the downstream target gene of TGF‐β1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS‐2B cells were cultured and exposed to recombinant soluble human TGF‐β1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA‐challenged mice, as well as TGF‐β1‐induced apoptosis and EMT of BEAS‐2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF‐β1 up‐regulated EMT related protein levels (N‐cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF‐β1‐induced N‐cadherin and Snail up‐regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF‐β1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF‐β1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

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“…IL-13 is required to the development of asthma [20] and induces different biological effects in airway in ammatory and structural cells [21]. More importantly, IL-13 is central to the pathogenesis of airway remodeling of asthma by acting on airway epithelial cells [22,23], broblasts [6], ASMCs [21] and induces goblet cell metaplasia, mucus hypersecretion, ASMCs proliferation and migration, broblasts proliferation, airway hyperreactivity and elevated IgE levels [21], all features of airway remodeling. We have previously shown that IL-13 upregulated Orai1 and STIM1 expression and SOCE in cultured ASMCs [8], consistent with the results in the current study that IL-13 dose-dependently increased the mRNA and protein expression of Orai1 in hBSMCs.…”

Section: Discussionmentioning

confidence: 99%

Role of LncRNA H19/miR-93-5p/Orai1 axis in the regulation of human bronchial smooth muscle cell functions and airway remodeling in murine models of asthma

Xiang¹,

Wan²,

Wang³

et al. 2021

Preprint

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Background Type 2 cytokine Interleukin (IL)-13 regulates airway remodeling in asthma by acting on store-operated Ca2+ entry (SOCE) in airway smooth muscle cells. The underlying mechanisms of this regulating effect of IL-13 are not fully understood. Methods Bioinformatic analysis identified interactions of microRNA 93-5p with Orai1, the pore-forming molecule of SOCE, and long non-coding RNA H19 respectively. We investigated the role of H19/miR-93-5p/Orai1 axis in the regulation of proliferation and migration of in vitro cultured human bronchial smooth muscle cells (hBSMCs) induced by IL-13. Functional relevance of H19 in airway inflammation and airway remodeling was investigated in acute and chronic murine models of asthma. Results IL-13 dose-dependently increased the expression of H19 and Orai1 and decreased the expression of miR-93-5p in hBSMCs; H19 siRNA reversed IL-13-induced miR-93-5p and Orai1 expression, and the proliferation and migration of hBSMCs. IL-13-promoted expression of H19 and Orai1 was reduced by miR-93-5p mimic and enhanced by miR-93-5p inhibitor. IL-13-promoted hBSMCs proliferation was enhanced by miR-93-5p inhibitor but not changed by miR-93-5p mimic; whereas IL-13-promoted hBSMCs migration was enhanced by miR-93-5p inhibitor and reduced by miR-93-5p mimic. MiR-93-5p mimic enhanced the inhibiting effect of H19 siRNA on IL-13-induced Orai1 mRNA expression, whereas miR-93-5p inhibitor reversed the inhibiting effects of H19 siRNA on IL-13-induced H19 and Orai1 mRNA and protein expression. The inhibiting effect of H19 siRNA on IL-13-induced hBSMCs proliferation and migration was reversed by miR-93-5p inhibitor but not changed by miR-935p mimic. In the lungs of both asthma mice models, the expression of H19 and Orai1 was higher than in control mice. In acute asthma mice, H19 siRNA reduced Orai1 expression, inflammatory cell infiltration and goblet cell hyperplasia in the lungs, and IL-13 levels in the bronchoalveolar lavage fluid. In chronic asthma mice, H19 siRNA reduced Orai1 expression, inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition and smooth muscle mass in the lungs, as well as IL-13 levels in the BALF. Conclusion IL-13 increases the proliferation and migration of airway smooth muscle cells by acting on H19/miR-93-5p/Orai1 axis, which also regulates airway inflammation and airway remodeling in murine models of asthma.

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IL‐13 signaling through IL‐13 receptor α2 mediates airway epithelial wound repair

Cited by 21 publications

References 54 publications

IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory

IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Role of LncRNA H19/miR-93-5p/Orai1 axis in the regulation of human bronchial smooth muscle cell functions and airway remodeling in murine models of asthma

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