更新于：2024-11-01

ENaC x Mucin

更新于：2024-11-01

基本信息

关联

项与 ENaC x Mucin 相关的药物

VS-024

靶点

ENaC x Mucin

作用机制

ENaC调节剂 [+2]

在研机构

Nuvara Therapeutics

原研机构

University of Florida Research Foundation, Inc.

在研适应症

慢性阻塞性肺疾病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 ENaC x Mucin 相关的临床结果

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100 项与 ENaC x Mucin 相关的转化医学

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0 项与 ENaC x Mucin 相关的专利（医药）

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项与 ENaC x Mucin 相关的文献（医药）

2001-01-01·Life Sciences3区 · 医学

Changes in expression of ion channels and aquaporins mRNA during differentiation in normal human nasal epithelial cells

3区 · 医学

Article

作者: Y.S. Kim ; J.S. Jung ; M.A. Yoo ; H.J. Roh ; E.S. Jun

Integrity of the airway epithelium is important for pulmonary defense mechanisms to infection. The lining of the airway contains a diverse population of cell types. Understanding about progenitor-progeny relationships during renewal of airway epithelium is important for elucidating mechanisms of injury repair or oncogenesis. Primary culture of airway epithelia is a good model for studying differentiation process of epithelial cells. Ion channels and aquaporins(AQPs) play a critical role on ion and fluid transport across airway epithelia. However, changes in their expression during differentiation of airway epithelial cells have not been reported yet. This study was undertaken to identify isoforms of aquaporins in cultured normal human nasal epithelial cells (NHNE) and effects of various culture conditions on expression of differentiation markers and channels. 1. Degenerative RT-PCR revealed that AQP3 and AQP4 are expressed in cultured NHNE cells. 2. Culture of NHNE cells on permeable filters induced expression of mucin, aquaporins and CFTR. 3. Retinoic acid induced morphological changes in NHNE cells and inhibited their proliferation. The treatment of retinoic acid induced expression of mucin and CFTR, whereas it inhibited expression of cornifin. The effect of retinoic acid was enhanced by culture of cells on permeable filters. 4. Dexamethasone induced ENaC expression in NHNE cells grown on permeable supports only, but did not affect expression of mucin, aquaporins and CFTR. These results indicate that cultured NHNE cells express aquaporins (AQP3 and 4), CFTR and ENaC, and culture of NHNE cells on permeable filters induces differentiation in to mucosecretory and surface epithelial cells, and that effects of retinoic acid and dexamethasone on gene expression are affected by culture conditions.

Scientific Reports

Inhibition of lipopolysaccharide-induced inflammation by trophoblast-conditioned medium and trophoblast-derived extracellular vesicles in human middle ear epithelial cells

Article

作者: Song, Jae-Jun ; Go, Yoon Young ; Lee, Chan Mi

AbstractOtitis media is a common disease but can cause severe inner ear inflammation and hearing loss if it persists for more than two weeks. This study elucidates the inflammation-inhibiting efficacy of conditioned medium (CM) and extracellular vesicles (EVs) derived from human trophoblast (TB) cells in lipopolysaccharide (LPS)-induced human middle ear epithelial cells (HMEECs). TB-conditioned medium (TB-CM) reduced the inflammatory response and regulated mucin and epithelial sodium channel genes in LPS-induced HMEECs. The underlying mechanism of cell migration during inflammatory healing in LPS-induced HMEECs treated with TB-CM was determined by RNA-sequencing analysis. Specifically, the NF-κB pathway related to the copper metabolism MURR1 domain protein was studied and verified through siRNA. This elucidation of the anti-inflammatory effect of TB-CM and TB-derived EVs demonstrates their clinical potential to treat chronic inflammation.

International Journal of Molecular Sciences2区 · 生物学

Congenital Deletion of Nedd4-2 in Lung Epithelial Cells Causes Progressive Alveolitis and Pulmonary Fibrosis in Neonatal Mice

2区 · 生物学

ArticleOA

作者: Kawabe, Hiroshi ; Duerr, Julia ; Seyhan Agircan, Ayça ; Leitz, Dominik H. W. ; Dalpke, Alexander H. ; Zimmermann, Stefan ; Mulugeta, Surafel ; Mall, Marcus A. ; Beers, Michael F.

Recent studies found that expression of NEDD4-2 is reduced in lung tissue from patients with idiopathic pulmonary fibrosis (IPF) and that the conditional deletion of Nedd4-2 in lung epithelial cells causes IPF-like disease in adult mice via multiple defects, including dysregulation of the epithelial Na+ channel (ENaC), TGFβ signaling and the biosynthesis of surfactant protein-C proprotein (proSP-C). However, knowledge of the impact of congenital deletion of Nedd4-2 on the lung phenotype remains limited. In this study, we therefore determined the effects of congenital deletion of Nedd4-2 in the lung epithelial cells of neonatal doxycycline-induced triple transgenic Nedd4-2fl/fl/CCSP-rtTA2S-M2/LC1 mice, with a focus on clinical phenotype, survival, lung morphology, inflammation markers in BAL, mucin expression, ENaC function and proSP-C trafficking. We found that the congenital deletion of Nedd4-2 caused a rapidly progressive lung disease in neonatal mice that shares key features with interstitial lung diseases in children (chILD), including hypoxemia, growth failure, sterile pneumonitis, fibrotic lung remodeling and high mortality. The congenital deletion of Nedd4-2 in lung epithelial cells caused increased expression of Muc5b and mucus plugging of distal airways, increased ENaC activity and proSP-C mistrafficking. This model of congenital deletion of Nedd4-2 may support studies of the pathogenesis and preclinical development of therapies for chILD.