Activation of protease‐activated receptor‐2 disrupts vaginal epithelial barrier function

Li, Yan; Feng, Chong; Wei, Xing; Zhang, Jiyuan; Zan, Ronghua; Guo, Zheng; Yang, Xinmi; Zhai, Jianjun

doi:10.1002/cbin.10315

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…A similar phenomenon was found by previous studies. Li et al [2014b] reported that activation of PAR2 interfered with the vaginal epithelial barrier integrity. Another study found that the corneal epithelial barrier function could be altered by PAR2 activation [Li et al, 2014a].…”

Section: Discussionmentioning

confidence: 99%

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Proteinase‐Activated Receptor‐2 Modulates Ve‐Cadherin Expression to Affect Human Vascular Endothelial Barrier Function

Zhang

2017

J of Cellular Biochemistry

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Published data indicate that the protease-activated receptor (PAR) 2 is involved in the pathogenesis of some cardiovascular diseases; the underlying mechanism is to be further investigated. Ve-cadherin is a critical molecule in maintaining the endothelial barrier integrity. This study aims to investigate the role of PAR2 activation in compromising the cardiac endothelial barrier function. In this study, human umbilical vein endothelial cells (Huvec cells) were cultured into monolayers using as an in vitro model of barrier function. The transepithelial electric resistance (TER) and permeability to dextran were assessed as indicators of barrier function. The expression of Ve-cadherin in Huvec cells was assessed by real-time RT-PCR, Western blotting, and chromatin immunoprecipitation. The results showed that exposure to tryptase in the culture, the barrier function of the Huvec monolayers, was markedly compromised; the levels of Ve-cadherin, one of the tight junction proteins, were suppressed as well. This was mimicked by exposing Huvec monolayers to the active PAR2 peptides (PAR2AP). After exposing to PAR2AP, the levels of histone deacetylase (HDAC)11 were increased in the Huvec cells. HDAC11 formed a complex with the transcription factor of Ve-cadherin to attenuate the Erg gene transcription activities and suppressed the expression of Ve-cadherin. In conclusion, activation of PAR2 compromises the vascular endothelial barrier function by suppressing the expression of Ve-cadherin. J. Cell. Biochem. 118: 4587-4593, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

“…It is reported that the protease-activated receptor (PAR) 2 is associated with the epithelial barrier dysfunction [Li et al, 2014b]. PAR2 is a protein that in humans is encoded by the F2RL1 gene.…”

mentioning

confidence: 99%

Proteinase‐Activated Receptor‐2 Modulates Ve‐Cadherin Expression to Affect Human Vascular Endothelial Barrier Function

Zhang

2017

J of Cellular Biochemistry

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“…The effect of PAR2 on epithelial barrier function was initially studied in organs other than skin. PAR2 activation has been shown to typically disrupt epithelial barrier function in the intestines, cornea, vaginal epithelium, lung epithelium and glomerular endothelium . It is important to note that PAR2 may have tissue‐specific effects, as one study found PAR2 unexpectedly played a role in strengthening the feto‐maternal barrier in mice placentas, possibly via regulation of claudin‐1 …”

Section: Methods and Resultsmentioning

confidence: 99%

Update on protease‐activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases

Henehan

Benedetto

2019

Experimental Dermatology

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Protease‐activated receptor 2 (PAR2) is a transmembrane receptor expressed by multiple tissues, including skin, with rapidly expanding knowledge regarding its roles. In the skin, PAR2 has extensively documented effects in promoting Th2 inflammation and pruritus; and its role in atopic dermatitis continues to be thoroughly studied. Numerous new investigations have shown a more complex range of activities potentially related to dermatologic diseases. Goal of this review is to outline emerging effects of PAR2 activation in the skin other than those related to immunologic and pruritic functions. Specifically, this work seeks to summarize current knowledge (and gaps) of PAR2 as a regulator of epidermal barrier, keratinocyte differentiation, cutaneous tumorigenesis and pigmentation. Additional focus will be placed on possible involvement in dermatologic disease and emergence as a therapeutic target.

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“…Besides linking pain and inflammatory response, activation of PARs is linked to other homeostatic/allostatic functions relevant to vulvodynia (i.e., vascular permeability 22–24 and synaptic plasticity) 23 . There is also evidence that activation of PAR2 by mast cell tryptase in vitro can compromise the barrier function of vaginal epithelial cells 25,26 . Together, these observations have led to recognition of the critical contribution of the neuroimmune system via PARs to neuroinflammation-associated diseases and the impetus to develop agents to treat such diseases by blocking PARS 27 .…”

Section: Discussionmentioning

confidence: 99%

“…23 There is also evidence that activation of PAR2 by mast cell tryptase in vitro can compromise the barrier function of vaginal epithelial cells. 25,26 Together, these observations have led to recognition of the critical contribution of the neuroimmune system via PARs to neuroinflammation-associated diseases and the impetus to develop agents to treat such diseases by blocking PARS. 27 However, developing effective inhibitors specific to any of the many known functions is proving to be challenging because of the complexity of the PARS regulation.…”

Section: Antiproteasesmentioning

confidence: 99%

A Pilot Proteomic Study of Vestibular Fluid From Patients With Vulvodynia

MacNeill

Umstead

Shearer

et al. 2022

J Low Genit Tract Dis

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Objective: Many women are affected by vulvodynia, but medical therapies to date have proven ineffective. We performed a pilot study using gel-based proteomics to develop a map of proteins present in vaginal/vestibular secretions and identify proteins that could be considered for future evaluation as potential therapeutic targets. Materials and Methods:We collected vestibular fluid from 4 controls and 4 patients with vulvodynia by placing a cotton swab in the vestibule and extracting the absorbed proteins. The proteins underwent 2-dimensional difference gel electrophoresis and mass spectrometry to develop a protein map. Immunohistochemistry was used to validate proteomic findings.Results: A map was constructed of 32 of the more abundant proteins in vestibular fluid and their levels compared in control subjects and vulvodynia patients. Among these were annexin A1, interleukin 1 receptor antagonist, protein S100 A9, and a number of antiproteases and proteases. Many of these proteins differed by at least 50% between groups, but only annexin A1, one of the protease inhibitors, and immunoglobulin G κ chain were significantly different. The results with annexin A1 were validated by similar findings with immunohistochemistry. Conclusions:The findings of this pilot study demonstrate a set of vestibule mucosa proteins that differ significantly-either increasing or decreasing-in vulvodynia patients compared with controls, and several others that exhibited greater than 1.5-fold change but did not reach statistical significance. This study constitutes a proof-of-principle that an open, unbiased proteomic approach can identify molecular participants in vulvodynia, some of which had not been identified to date by hypothesis-driven studies.

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Activation of protease‐activated receptor‐2 disrupts vaginal epithelial barrier function

Cited by 9 publications

References 22 publications

Proteinase‐Activated Receptor‐2 Modulates Ve‐Cadherin Expression to Affect Human Vascular Endothelial Barrier Function

Proteinase‐Activated Receptor‐2 Modulates Ve‐Cadherin Expression to Affect Human Vascular Endothelial Barrier Function

Update on protease‐activated receptor 2 in cutaneous barrier, differentiation, tumorigenesis and pigmentation, and its role in related dermatologic diseases

A Pilot Proteomic Study of Vestibular Fluid From Patients With Vulvodynia

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