Protein Kinase D Promotes Airway Epithelial Barrier Dysfunction and Permeability through Down-regulation of Claudin-1

Gan, Huachen; Wang, Guibo; Qin, Hao; Wang, Q. Jane; Tang, Hua

doi:10.1074/jbc.m113.511527

Cited by 26 publications

(20 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, different strategies may be required to reverse the chronic structural changes in the airway epithelium and subepithelial layers in asthma. As both viral mimic poly-(I:C) and RSV have been shown to disrupt barrier function of human bronchial epithelium by activation of protein kinase D [45,98], possibly through down-regulation of claudin-1 [99], this pathway may constitute a novel therapeutic target to restore barrier function, especially upon viral infection. Furthermore, as outlined above, caveolin-1 may be a promising molecular target in the improvement of epithelial integrity [21].…”

Section: Therapeutic Strategies To Improve Barrier Functionmentioning

confidence: 99%

Airway epithelial barrier function regulates the pathogenesis of allergic asthma

Heijink

Nawijn

Hackett

2014

Clin Experimental Allergy

105

View full text Add to dashboard Cite

The integrity of the airway epithelium in patients with asthma is often disrupted, with loss of epithelial cell-cell contacts. Airway epithelial barrier dysfunction may have important implications for asthma, because structural epithelial barrier function is tightly interwoven with the ability of the epithelium to regulate the immune system. We propose that changes at the airway epithelial barrier play a central role in the sensitisation to allergens and pathogenesis of allergic asthma. Many of the recently identified susceptibility genes for asthma are expressed in airway epithelium. However, the exact mechanisms by which the expression of epithelial susceptibility genes translates into a functionally altered response to aeroallergens in asthma are still unknown. In this review, we will focus on the role of airway epithelial barrier function in the susceptibility to develop allergic asthma and discuss therapeutic strategies aimed at the epithelial barrier.

show abstract

Section: Therapeutic Strategies To Improve Barrier Functionmentioning

confidence: 99%

Airway epithelial barrier function regulates the pathogenesis of allergic asthma

Heijink

Nawijn

Hackett

2014

Clin Experimental Allergy

105

View full text Add to dashboard Cite

show abstract

“…Altered functions of claudins are associated with different forms of cancer, inflammatory bowel diseases and diarrhea ( 4 ). Claudin-1, a major structural and functional TJ protein is responsible for modulating the permeability of the epidermis ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

The possible association between AQP9 in the intestinal epithelium and acute liver injury‑induced intestinal epithelium damage

Xiang

Wen

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

The present study aimed to investigate the expression and function of aquaporin (AQP)9 in the intestinal tract of acute liver injury rat models. A total of 20 Sprague Dawley rats were randomly divided into four groups: Normal control (NC) group and acute liver injury groups (24, 48 and 72 h). Acute liver injury rat models were established using D-amino galactose, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil) and albumin were determined using an automatic biochemical analyzer. Proteins levels of myosin light chain kinase (MLCK) in rat intestinal mucosa were investigated via immunohistochemistry. Pathological features were observed using hematoxylin and eosin (H&E) staining. MLCK, AQP9 and claudin-1 protein expression levels were detected via western blotting. Levels of ALT and AST in acute liver injury rats were revealed to steadily increase between 24 and 48 h time intervals, reaching a peak level at 48 h. Furthermore, TBil levels increased significantly until 72 h. Levels of ALT were revealed to significantly increase until the 48 h time interval, and then steadily decreased until the 72 h time interval. The acute liver injury 72 h group exhibited the greatest levels of MLCK expression among the three acute liver injury groups; however, all three acute liver injury groups exhibited enhanced levels of MLCK expression compared with the NC group. Protein levels of AQP9 and claudin-1 were enhanced in the NC group compared with the three acute liver injury groups. H&E staining demonstrated that terminal ileum mucosal layer tissues obtained from the acute liver injury rats exhibited visible neutrophil infiltration. Furthermore, the results revealed that levels of tumor necrosis factor-α, interleukin (IL)-6 and IL-10 serum cytokines were significantly increased in the acute liver injury groups. In addition, AQP9 protein expression was suppressed in acute liver injury rats, which induced pathological alterations in terminal ileum tissues may be associated with changes of claudin-1 and MLCK protein levels.

show abstract

“…Other cytokines, such as tumor necrosis factor (TNF)-α, via Src kinases activation, concur to determining the barrier dysfunction observed in chronic airways diseases (Hardyman et al, 2013 ). The consequence is a chronic, self-sustained wound scenario dominated by the secretion of secondary stress growth factors (Heijink et al, 2012 ; Gan et al, 2013 ; Hardyman et al, 2013 ) which fuel the progression of airway wall remodeling (Boxall et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Soft TCPTP Agonism—Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine

et al. 2016

View full text Add to dashboard Cite

A reparative approach of disrupted epithelium in obstructive airway diseases, namely asthma and chronic obstructive pulmonary disease (COPD), may afford protection and long-lasting results compared to conventional therapies, e.g., corticosteroids or immunosuppressant drugs. Here, we propose the polyamine spermidine as a novel therapeutic agent in airways diseases, based on a recently identified mode of action: T-cell protein tyrosine phosphatase (TCPTP) agonism. It may include and surpass single-inhibitors of stress and secondary growth factor pathway signaling, i.e., the new medicinal chemistry in lung diseases. Enhanced polyamine biosynthesis has been charged with aggravating prognosis by competing for L-arginine at detriment of nitric oxide (NO) synthesis with bronchoconstrictive effects. Although excess spermine, a higher polyamine, is harmful to airways physiology, spermidine can pivot the cell homeostasis during stress conditions by the activation of TCPTP. In fact, the dephosphorylating activity of TCPTP inhibits the signaling cascade that leads to the expression of genes involved in detachment and epithelial-to-mesenchymal transition (EMT), and increases the expression of adhesion and tight junction proteins, thereby enhancing the barrier functionality in inflammation-prone tissues. Moreover, a further beneficial effect of spermidine may derive from its ability to promote autophagy, possibly in a TCPTP-dependent way. Since doses of spermidine in the micromolar range are sufficient to activate TCPTP, low amounts of spermidine administered in sustained release modality may provide an optimal pharmacologic profile for the treatment of obstructive airway diseases.

show abstract

Protein Kinase D Promotes Airway Epithelial Barrier Dysfunction and Permeability through Down-regulation of Claudin-1

Cited by 26 publications

References 58 publications

Airway epithelial barrier function regulates the pathogenesis of allergic asthma

Airway epithelial barrier function regulates the pathogenesis of allergic asthma

The possible association between AQP9 in the intestinal epithelium and acute liver injury‑induced intestinal epithelium damage

Soft TCPTP Agonism—Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine

Contact Info

Product

Resources

About