Role of Ezrin in Asthma-Related Airway Inflammation and Remodeling

Zhao, Shu-Mei; Luo, Jia‐Qi; Hu, Jun; Wang, Hesheng; Zhao, Ningwei; Cao, Meng; Zhang, Cong; Hu, Rongkui; Liu, Lanying

doi:10.1155/2022/6255012

Cited by 4 publications

(4 citation statements)

References 127 publications

(160 reference statements)

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“…Zhao et al. 36 showed that the Ezrin phosphorylation limited the production of IL‐10 in B cells. Shan et al.…”

Section: Discussionmentioning

confidence: 99%

“…Ding et al 35 found that Ezrin promoted the generation of inflammatory factors TNFα, IL-1β and HMGB1. Zhao et al 36 showed that the Ezrin phosphorylation limited the production of IL-10 in B cells. Shan et al 37 believed that the cytoskeleton interaction mediated the mitochondrial dynamics and localization.…”

Section: Discussionmentioning

confidence: 99%

“…found that Ezrin promoted the generation of inflammatory factors TNF‐α, IL‐1β and HMGB1. Zhao et al 36 . showed that the Ezrin phosphorylation limited the production of IL‐10 in B cells.…”

Section: Discussionmentioning

confidence: 99%

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Celastrol alleviates atopic dermatitis by regulating Ezrin‐mediated mitochondrial fission and fusion

Wang,

Jin,

Liu

et al. 2024

J Cellular Molecular Medi

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Celastrol, a bioactive molecule extracted from the plant Tripterygium wilfordii Hook F., possesses anti‐inflammatory, anti‐obesity and anti‐tumour properties. Despite its efficacy in improving erythema and scaling in psoriatic mice, the specific therapeutic mechanism of celastrol in atopic dermatitis (AD) remains unknown. This study aims to examine the role and mechanism of celastrol in AD using TNF‐α‐stimulated HaCaT cells and DNCB‐induced Balb/c mice as in vitro and in vivo AD models, respectively. Celastrol was found to inhibit the increased epidermal thickness, reduce spleen and lymph node weights, attenuate inflammatory cell infiltration and mast cell degranulation and decrease thymic stromal lymphopoietin (TSLP) as well as various inflammatory factors (IL‐4, IL‐13, TNF‐α, IL‐5, IL‐31, IL‐33, IgE, TSLP, IL‐17, IL‐23, IL‐1β, CCL11 and CCL17) in AD mice. Additionally, celastrol inhibited Ezrin phosphorylation at Thr567, restored mitochondrial network structure, promoted translocation of Drp1 to the cytoplasm and reduced TNF‐α‐induced cellular reactive oxygen species (ROS), mitochondrial ROS (mtROS) and mitochondrial membrane potential (MMP) production. Interestingly, Mdivi‐1 (a mitochondrial fission inhibitor) and Ezrin‐specific siRNAs lowered inflammatory factor levels and restored mitochondrial reticular formation, as well as ROS, mtROS and MMP production. Co‐immunoprecipitation revealed that Ezrin interacted with Drp1. Knocking down Ezrin reduced mitochondrial fission protein Drp1 phosphorylation and Fis1 expression while increasing the expression of fusion proteins Mfn1 and Mfn2. The regulation of mitochondrial fission and fusion by Ezrin was confirmed. Overall, celastrol may alleviate AD by regulating Ezrin‐mediated mitochondrial fission and fusion, which may become a novel therapeutic reagent for alleviating AD.

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“…Zhao et al. 36 showed that the Ezrin phosphorylation limited the production of IL‐10 in B cells. Shan et al.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Celastrol alleviates atopic dermatitis by regulating Ezrin‐mediated mitochondrial fission and fusion

Wang,

Jin,

Liu

et al. 2024

J Cellular Molecular Medi

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“…Even though ezrin has been mostly discussed for its involvement in cancer [167], it is not known if ezrin could compensate for moesin should the latter be absent or "incapacitated" in mast cells. In fact, ezrin, has been implicated in asthma [168]. The phosphorylation of ezrin at Thr567 was associated with trophoblast motility [169].…”

Section: Moesin In Mast Cellsmentioning

confidence: 99%

Potential Role of Moesin in Regulating Mast Cell Secretion

Kempuraj

2023

IJMS

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Mast cells have existed for millions of years in species that never suffer from allergic reactions. Hence, in addition to allergies, mast cells can play a critical role in homeostasis and inflammation via secretion of numerous vasoactive, pro-inflammatory and neuro-sensitizing mediators. Secretion may utilize different modes that involve the cytoskeleton, but our understanding of the molecular mechanisms regulating secretion is still not well understood. The Ezrin/Radixin/Moesin (ERM) family of proteins is involved in linking cell surface-initiated signaling to the actin cytoskeleton. However, how ERMs may regulate secretion from mast cells is still poorly understood. ERMs contain two functional domains connected through a long α-helix region, the N-terminal FERM (band 4.1 protein-ERM) domain and the C-terminal ERM association domain (C-ERMAD). The FERM domain and the C-ERMAD can bind to each other in a head-to-tail manner, leading to a closed/inactive conformation. Typically, phosphorylation on the C-terminus Thr has been associated with the activation of ERMs, including secretion from macrophages and platelets. It has previously been shown that the ability of the so-called mast cell “stabilizer” disodium cromoglycate (cromolyn) to inhibit secretion from rat mast cells closely paralleled the phosphorylation of a 78 kDa protein, which was subsequently shown to be moesin, a member of ERMs. Interestingly, the phosphorylation of moesin during the inhibition of mast cell secretion was on the N-terminal Ser56/74 and Thr66 residues. This phosphorylation pattern could lock moesin in its inactive state and render it inaccessible to binding to the Soluble NSF attachment protein receptors (SNAREs) and synaptosomal-associated proteins (SNAPs) critical for exocytosis. Using confocal microscopic imaging, we showed moesin was found to colocalize with actin and cluster around secretory granules during inhibition of secretion. In conclusion, the phosphorylation pattern and localization of moesin may be important in the regulation of mast cell secretion and could be targeted for the development of effective inhibitors of secretion of allergic and inflammatory mediators from mast cells.

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