scholarly journals RBFOX3 regulates Claudin-1 expression in human lung tissue via attenuation of proteasomal degradation

2017 ◽  
Vol 37 (1) ◽  
Author(s):  
Yong-Eun Kim ◽  
Sunkyung Choi ◽  
Jong Ok Kim ◽  
Kee K. Kim
Keyword(s):  
Lung Tissue ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Rna Binding ◽  
Human Lung ◽  
Human Lung Cancer ◽  
Mrna Levels ◽  
Human Lung Tissue ◽  
Protein Levels ◽  
The Stability

RBFOX3, a nuclear RNA-binding protein, is well known as a regulator of alternative pre-mRNA splicing during neuronal development. However, other functions of RBFOX3 are poorly understood. Here, we investigated the function of RBFOX3 in the cytoplasm with respect to regulation of Claudin-1 expression. In human lung tissue, Claudin-1 is higher in RBFOX3-positive cells than in RBFOX3-negative cells. Immunostaining and mRNA quantification revealed that protein levels, but not mRNA levels, of Claudin-1 are increased by RBFOX3. In addition, cycloheximide treatment of human lung cancer cells revealed that RBFOX3 increases the stability of Claudin-1 through attenuation of its ubiquitination. Our study provides insights into the molecular mechanisms by which RBFOX3 regulates Claudin-1 expression in human lung tissue.

Ontogeny of the eotaxins in human lung

2008 ◽  
Vol 294 (2) ◽  
pp. L214-L224 ◽  
Author(s):  
Kathleen J. Haley ◽  
Mary E. Sunday ◽  
Yolanda Porrata ◽  
Colleen Kelley ◽  
Anne Twomey ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lung Tissue ◽  
Human Lung ◽  
Airway Epithelial Cells ◽  
Pcr Analysis ◽  
Mrna Levels ◽  
Airway Epithelial ◽  
Human Lung Tissue ◽  
Qrt Pcr ◽  
Explant Cultures

The ontogeny of the C-C chemokines eotaxin-1, eotaxin-2, and eotaxin-3 has not been fully elucidated in human lung. We explored a possible role for eotaxin in developing lung by determining the ontogeny of eotaxin-1 (CCL11), eotaxin-2 (CCL24), eotaxin-3 (CCL26), and the eotaxin receptor, CCR3. We tested discarded surgical samples of developing human lung tissue using quantitative RT-PCR (QRT-PCR) and immunostaining for expression of CCL11, CCL24, CCL26, and CCR3. We assessed possible functionality of the eotaxin-CCR3 system by treating lung explant cultures with exogenous CCL11 and analyzing the cultures for evidence of changes in proliferation and activation of ERK1/2, a signaling pathway associated with CCR3. QRT-PCR analyses of 22 developing lung tissue samples with gestational ages 10–23 wk demonstrated that eotaxin-1 mRNA is most abundant in developing lung, whereas mRNAs for eotaxin-2 and eotaxin-3 are minimally detectable. CCL11 mRNA levels correlated with gestational age ( P < 0.05), and immunoreactivity was localized predominantly to airway epithelial cells. QRT-PCR analysis detected CCR3 expression in 16 of 19 developing lung samples. Supporting functional capacity in the immature lung, CCL11 treatment of lung explant cultures resulted in significantly increased ( P < 0.05) cell proliferation and activation of the ERK signaling pathway, which is downstream from CCR3, suggesting that proliferation was due to activation of CCR3 receptors by CCL11. We conclude that developing lung expresses the eotaxins and functional CCR3 receptor. CCL11 may promote airway epithelial proliferation in the developing lung.

scholarly journals Role of Human Antigen R (HuR) in the Regulation of Pulmonary ACE2 Expression

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 22
Author(s):  
Noof Aloufi ◽  
Zahraa Haidar ◽  
Jun Ding ◽  
Parameswaran Nair ◽  
Andrea Benedetti ◽  
...  
Keyword(s):  
Protein Expression ◽  
Lung Tissue ◽  
Cellular Localization ◽  
Rna Binding ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Severe Illness ◽  
Protein Levels ◽  
Human Lung Cells ◽  
Increased Risk

Patients with COPD may be at an increased risk for severe illness from COVID-19 because of ACE2 upregulation, the entry receptor for SARS-CoV-2. Chronic exposure to cigarette smoke, the main risk factor for COPD, increases pulmonary ACE2. How ACE2 expression is controlled is not known but may involve HuR, an RNA binding protein that increases protein expression by stabilizing mRNA. We hypothesized that HuR would increase ACE2 protein expression. We analyzed scRNA-seq data to profile ELAVL1 expression in distinct respiratory cell populations in COVID-19 and COPD patients. HuR expression and cellular localization was evaluated in COPD lung tissue by multiplex immunohistochemistry and in human lung cells by imaging flow cytometry. The regulation of ACE2 expression was evaluated using siRNA-mediated knockdown of HuR. There is a significant positive correlation between ELAVL1 and ACE2 in COPD cells. HuR cytoplasmic localization is higher in smoker and COPD lung tissue; there were also higher levels of cleaved HuR (CP-1). HuR binds to ACE2 mRNA but knockdown of HuR does not change ACE2 protein levels in primary human lung fibroblasts (HLFs). Our work is the first to investigate the association between ACE2 and HuR. Further investigation is needed to understand the mechanistic underpinning behind the regulation of ACE2 expression.

scholarly journals AZGP1 mRNA levels in normal human lung tissue correlate with lung cancer disease status

Oncogene ◽  
2007 ◽  
Vol 27 (11) ◽  
pp. 1650-1656 ◽  
Author(s):  
F S Falvella ◽  
M Spinola ◽  
C Pignatiello ◽  
S Noci ◽  
B Conti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Tissue ◽  
Human Lung ◽  
Disease Status ◽  
Mrna Levels ◽  
Human Lung Tissue ◽  
Cancer Disease ◽  
Normal Human

scholarly journals Loss of Aly/ALYREF Suppresses Toxicity in Both Tau and TDP-43 Models of Neurodegeneration

2021 ◽  
Author(s):  
Rebecca Kow ◽  
Aristide Black ◽  
Aleen Saxton ◽  
Nicole Liachko ◽  
Brian Kraemer
Keyword(s):  
Nuclear Export ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Mrna Levels ◽  
Tau Pathology ◽  
Human Cell Culture ◽  
Behavioral Deficits ◽  
C Elegans ◽  
Protein Levels ◽  
Binding Protein Gene

Abstract Background Neurodegenerative diseases with tau pathology, or tauopathies, include Alzheimer’s Disease and related dementia disorders. Previous work has shown that loss of the poly(A) RNA-binding protein gene sut2/MSUT2 strongly suppressed tauopathy in C. elegans, human cell culture, and mouse models of tauopathy. However, the mechanism of suppression is still unclear. Recent work has shown that MSUT2 protein interacts with the THO complex and ALYREF, which are components of the mRNA nuclear export complex. Additionally, previous work showed ALYREF homolog Ref1 modulates TDP-43 and G 4 C 2 toxicity in D. melanogaster models. Methods We used transgenic C. elegans models of tau or TDP-43 toxicity to investigate the effects of loss of ALYREF function on tau and TDP-43 toxicity. In C. elegans, there are three genes that are homologous to human ALYREF: aly-1, aly-2, and aly-3. Results We found that loss of C. elegans aly gene function, especially loss of both aly-2 and aly-3, suppressed tau-induced toxic phenotypes. Loss of aly-2 and aly-3 was also able to suppress TDP-43-induced behavioral deficits. However, loss of aly-2 and aly-3 had divergent effects on mRNA and protein levels as total tau protein levels were reduced while mRNA levels were increased, but no significant effects were seen on total TDP-43 protein or mRNA levels. Conclusions Our results suggest that although aly genes modulate both tau and TDP-43-induced toxicity phenotypes, the molecular mechanisms of suppression are different and separated from impacts on mRNA and protein levels. Altogether this study highlights the importance of elucidating RNA-related mechanisms in both tau and TDP-43-induced toxicity.

scholarly journals RNA–Binding Protein HuD as a Versatile Factor in Neuronal and Non–Neuronal Systems

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 361
Author(s):  
Myeongwoo Jung ◽  
Eun-Kyung Lee
Keyword(s):  
Gene Expression ◽  
Neural Plasticity ◽  
Molecular Mechanisms ◽  
Neuronal Development ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Novel Treatments ◽  
Target Mrnas ◽  
Neuronal Systems

HuD (also known as ELAVL4) is an RNA–binding protein belonging to the human antigen (Hu) family that regulates stability, translation, splicing, and adenylation of target mRNAs. Unlike ubiquitously distributed HuR, HuD is only expressed in certain types of tissues, mainly in neuronal systems. Numerous studies have shown that HuD plays essential roles in neuronal development, differentiation, neurogenesis, dendritic maturation, neural plasticity, and synaptic transmission by regulating the metabolism of target mRNAs. However, growing evidence suggests that HuD also functions as a pivotal regulator of gene expression in non–neuronal systems and its malfunction is implicated in disease pathogenesis. Comprehensive knowledge of HuD expression, abundance, molecular targets, and regulatory mechanisms will broaden our understanding of its role as a versatile regulator of gene expression, thus enabling novel treatments for diseases with aberrant HuD expression. This review focuses on recent advances investigating the emerging role of HuD, its molecular mechanisms of target gene regulation, and its disease relevance in both neuronal and non–neuronal systems.

scholarly journals DBC1 (Deleted in Breast Cancer 1) modulates the stability and function of the nuclear receptor Rev-erbα

2013 ◽  
Vol 451 (3) ◽  
pp. 453-461 ◽  
Author(s):  
Claudia C. S. Chini ◽  
Carlos Escande ◽  
Veronica Nin ◽  
Eduardo N. Chini
Keyword(s):  
Breast Cancer ◽  
Nuclear Receptor ◽  
Clock Genes ◽  
Mrna Levels ◽  
Protein Levels ◽  
The Stability ◽  
And Function ◽  
Interfering Rna ◽  
In Cells

The nuclear receptor Rev-erbα has been implicated as a major regulator of the circadian clock and integrates circadian rhythm and metabolism. Rev-erbα controls circadian oscillations of several clock genes and Rev-erbα protein degradation is important for maintenance of the circadian oscillations and also for adipocyte differentiation. Elucidating the mechanisms that regulate Rev-erbα stability is essential for our understanding of these processes. In the present paper, we report that the protein DBC1 (Deleted in Breast Cancer 1) is a novel regulator of Rev-erbα. Rev-erbα and DBC1 interact in cells and in vivo, and DBC1 modulates the Rev-erbα repressor function. Depletion of DBC1 by siRNA (small interfering RNA) in cells or in DBC1-KO (knockout) mice produced a marked decrease in Rev-erbα protein levels, but not in mRNA levels. In contrast, DBC1 overexpression significantly enhanced Rev-erbα protein stability by preventing its ubiquitination and degradation. The regulation of Rev-erbα protein levels and function by DBC1 depends on both the N-terminal and C-terminal domains of DBC1. More importantly, in cells depleted of DBC1, there was a dramatic decrease in circadian oscillations of both Rev-erbα and BMAL1. In summary, our data identify DBC1 as an important regulator of the circadian receptor Rev-erbα and proposes that Rev-erbα could be involved in mediating some of the physiological effects of DBC1.

Mast Cell Heterogeneity in Human Lung Tissue

1989 ◽  
Vol 77 (3) ◽  
pp. 297-304 ◽  
Author(s):  
F. J. Van Overveld ◽  
L. A. M. J. Houben ◽  
F. E. M. Schmitz du Moulin ◽  
P. L. B. Bruijnzeel ◽  
J. A. M. Raaijmakers ◽  
...  
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Alcian Blue ◽  
Lung Tissue ◽  
Human Lung ◽  
Immunoglobulin E ◽  
Prostaglandin D2 ◽  
Leukotriene C4 ◽  
Human Lung Tissue ◽  
No Release

1. In this study mast cells were found to comprise 2.1% of total cells recovered by enzymatic digestion of human lung tissue. 2. This mast cell population consisted of 79% formalin-sensitive, Alcian Blue-positive mast cells and 21% formalin-insensitive, Alcian Blue-positive mast cells. 3. By the use of centrifugal elutriation and subsequent Percoll gradient centrifugation, separate mixed cell populations could be obtained in which the mast cell constituents were either of the formalin-sensitive or -insensitive type. 4. Cell suspensions in which formalin-sensitive cells comprised 97% of mast cells contained approximately 1.34 pg of histamine per mast cell, whereas in preparations in which mast cells were 84% formalin-resistant the histamine content was approximately 4.17 pg of histamine per mast cell. 5. The histamine release upon anti-immunoglobulin E challenge of formalin-sensitive mast cells was greater than the release by formalin-insensitive mast cells. 6. After challenge with opsonized zymosan, only formalin-sensitive mast cells were able to release histamine. 7. Leukotriene C4 release was observed when formalin-sensitive mast cells were challenged with antiimmunoglobulin E. Formalin-insensitive mast cells showed no release of leukotriene C4. 8. Prostaglandin D2 release was observed when formalin-insensitive mast cells were challenged with antiimmunoglobulin E. Formalin-sensitive mast cells showed no release of prostaglandin D2.

The Glucocorticosteroid, Budesonide, Partially Blocks Histamine Release from Human Lung Tissue in Vitro

Allergy ◽  
1986 ◽  
Vol 41 (5) ◽  
pp. 319-326 ◽  
Author(s):  
H. Bergstrand ◽  
B. Lundquist ◽  
B.-Å. Petersson
Keyword(s):  
Histamine Release ◽  
Lung Tissue ◽  
Human Lung ◽  
Human Lung Tissue

scholarly journals PRMT5 Promotes EMT Through Regulating Akt Activity in Human Lung Cancer

2021 ◽  
Vol 30 ◽  
pp. 096368972110017
Author(s):  
Jianhao Huang ◽  
Yonghua Zheng ◽  
Xiao Zheng ◽  
Bao Qian ◽  
Qi Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Akt Signaling ◽  
Lung Cancer Cells ◽  
Signaling Cascades ◽  
Human Lung Cancer ◽  
Mesenchymal Transition ◽  
Human Lung Cancer Cells

The type II protein arginine methyltransferase 5 (PRMT5) has been engaged in various human cancer development and progression types. Nevertheless, few studies uncover the biological functions of PRMT5 in the epithelial-mesenchymal transition (EMT) of human lung cancer cells, and the associated molecular mechanisms and signaling cascades are entirely unknown. Here, we show that PRMT5 is the ectopic expression in human lung cancer tissues and cell lines. Further study reveals that silencing PRMT5 by lentivirus-mediated shRNA or blocking of PRMT5 by specific inhibitor GSK591 attenuates the expression levels of EMT-related markers in vivo, using the xenograft mouse model. Moreover, our results show that down-regulation of PRMT5 impairs EGFR/Akt signaling cascades in human lung cancer cells, whereas re-expression of PRMT5 recovers those changes, suggesting that PRMT5 regulates EMT probably through EGFR/Akt signaling axis. Altogether, our results demonstrate that PRMT5 serves as a critical oncogenic regulator and promotes EMT in human lung cancer cells. More importantly, our findings also suggest that PRMT5 may be a potential therapeutic candidate for the treatment of human lung cancer.

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