scholarly journals An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans

Genes ◽  
2020 ◽  
Vol 11 (10) ◽  
pp. 1143
Author(s):  
Matthias F. Hulliger ◽  
Alicja Pacholewska ◽  
Amandine Vargas ◽  
Jean-Pierre Lavoie ◽  
Tosso Leeb ◽  
...  

Severe equine asthma is an incurable obstructive respiratory condition affecting 10–15% of horses in temperate climates. Upon exposure to airborne antigens from hay feeding, affected horses show neutrophilic airway inflammation and bronchoconstriction, leading to increased respiratory effort. The resulting implications range from welfare concerns to economic impacts on equestrian sports and horse breeding. Immunological and pathophysiological characteristics of severe equine asthma show important parallels with allergic and severe neutrophilic human asthma. Our study aimed at investigating regulatory networks underlying the pathophysiology of the disease by profiling miRNA and mRNA expression in lung tissue samples from asthmatic horses compared with healthy controls. We sequenced small RNAs and mRNAs from lungs of seven asthmatic horses in exacerbation, five affected horses in remission, and eight healthy control horses. Our comprehensive differential expression analyses, combined with the miRNA–mRNA negative correlation approach, revealed a strong similarity on the transcriptomic level between severe equine asthma and severe neutrophilic asthma in humans, potentially through affecting Th17 cell differentiation. This study also showed that several dysregulated miRNAs and mRNAs are involved in airway remodeling. These results present a starting point for a better transcriptomic understanding of severe equine asthma and its similarities to asthma in humans.

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. e151-e160 ◽  
Author(s):  
Soile Tuomela ◽  
Verna Salo ◽  
Subhash K. Tripathi ◽  
Zhi Chen ◽  
Kirsti Laurila ◽  
...  

Abstract Th17 cells play an essential role in the pathogenesis of autoimmune and inflammatory diseases. Most of our current understanding on Th17 cell differentiation relies on studies carried out in mice, whereas the molecular mechanisms controlling human Th17 cell differentiation are less well defined. In this study, we identified gene expression changes characterizing early stages of human Th17 cell differentiation through genome-wide gene expression profiling. CD4+ cells isolated from umbilical cord blood were used to determine detailed kinetics of gene expression after initiation of Th17 differentiation with IL1β, IL6, and TGFβ. The differential expression of selected candidate genes was further validated at protein level and analyzed for specificity in initiation of Th17 compared with initiation of other Th subsets, namely Th1, Th2, and iTreg. This first genome-wide profiling of transcriptomics during the induction of human Th17 differentiation provides a starting point for defining gene regulatory networks and identifying new candidates regulating Th17 differentiation in humans.


2021 ◽  
Vol 22 (3) ◽  
pp. 1390
Author(s):  
Julia Mester-Tonczar ◽  
Patrick Einzinger ◽  
Johannes Winkler ◽  
Nina Kastner ◽  
Andreas Spannbauer ◽  
...  

Circular RNAs (circRNAs) are crucial in gene regulatory networks and disease development, yet circRNA expression in myocardial infarction (MI) is poorly understood. Here, we harvested myocardium samples from domestic pigs 3 days after closed-chest reperfused MI or sham surgery. Cardiac circRNAs were identified by RNA-sequencing of rRNA-depleted RNA from infarcted and healthy myocardium tissue samples. Bioinformatics analysis was performed using the CIRIfull and KNIFE algorithms, and circRNAs identified with both algorithms were subjected to differential expression (DE) analysis and validation by qPCR. Circ-RCAN2 and circ-C12orf29 expressions were significantly downregulated in infarcted tissue compared to healthy pig heart. Sanger sequencing was performed to identify the backsplice junctions of circular transcripts. Finally, we compared the expressions of circ-C12orf29 and circ-RCAN2 between porcine cardiac progenitor cells (pCPCs) that were incubated in a hypoxia chamber for different time periods versus normoxic pCPCs. Circ-C12orf29 did not show significant DE in vitro, whereas circ-RCAN2 exhibited significant ischemia-time-dependent upregulation in hypoxic pCPCs. Overall, our results revealed novel cardiac circRNAs with DE patterns in pCPCs, and in infarcted and healthy myocardium. Circ-RCAN2 exhibited differential regulation by myocardial infarction in vivo and by hypoxia in vitro. These results will improve our understanding of circRNA regulation during acute MI.


Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
De Xi ◽  
Lukas Hofmann ◽  
Thomas Alter ◽  
Ralf Einspanier ◽  
Stefan Bereswill ◽  
...  

Abstract Background Campylobacter jejuni (C. jejuni) infections are of increasing importance worldwide. As a typical mucosal pathogen, the interaction of C. jejuni with mucins is a prominent step in the colonisation of mucosal surfaces. Despite recent advances in understanding the interaction between bacterial pathogens and host mucins, the mechanisms of mucin glycosylation during intestinal C. jejuni infection remain largely unclear. This prompted us to identify relevant regulatory networks that are concerted by miRNAs and could play a role in the mucin modification and interaction. Results We firstly used a human intestinal in vitro model, in which we observed altered transcription of MUC2 and TFF3 upon C. jejuni NCTC 11168 infection. Using a combined approach consisting of in silico analysis together with in vitro expression analysis, we identified the conserved miRNAs miR-125a-5p and miR-615-3p associated with MUC2 and TFF3. Further pathway analyses showed that both miRNAs appear to regulate glycosyltransferases, which are related to the KEGG pathway ‘Mucin type O-glycan biosynthesis’. To validate the proposed interactions, we applied an in vivo approach utilising a well-established secondary abiotic IL-10−/− mouse model for infection with C. jejuni 81-176. In colonic tissue samples, we confirmed infection-dependent aberrant transcription of MUC2 and TFF3. Moreover, two predicted glycosyltransferases, the sialyltransferases ST3GAL1 and ST3GAL2, exhibited inversely correlated transcriptional levels compared to the expression of the identified miRNAs miR-125a-5p and miR-615-3p, respectively. In this study, we mainly focused on the interaction between miR-615-3p and ST3GAL2 and were able to demonstrate their molecular interaction using luciferase reporter assays and RNAi. Detection of ST3GAL2 in murine colonic tissue by immunofluorescence demonstrated reduced intensity after C. jejuni 81-176 infection and was thus consistent with the observations made above. Conclusions We report here for the first time the regulation of glycosyltransferases by miRNAs during murine infection with C. jejuni 81-176. Our data suggest that mucin type O-glycan biosynthesis is concerted by the interplay of miRNAs and glycosyltransferases, which could determine the shape of intestinal glycosylated proteins during infection.


2021 ◽  
Vol 22 (14) ◽  
pp. 7241
Author(s):  
Piotr K. Krajewski ◽  
Weronika Szukała ◽  
Agata Lichawska-Cieślar ◽  
Łukasz Matusiak ◽  
Jolanta Jura ◽  
...  

The pathogenesis of hidradenitis suppurativa (HS) is yet to be fully understood. However, inflammation is a key element in the development of skin lesions. The aim of this study was to evaluate the expression of monocyte chemotactic protein-1-induced protein-1 (MCPIP1) in the skin of patients suffering from HS. Skin biopsies of 15 patients with HS and 15 healthy controls were obtained and processed for immunohistochemistry, western blot, and real time PCR. The highest mean MCPIP1 mRNA expression was found in the inflammatory lesional skin of HS patients. It was significantly higher than MCPIP1 mRNA expression in the biopsies from both healthy controls and non-lesional skin of HS patients. Western blot analysis indicated that expression of MCPIP1 was elevated within both lesional and non-lesional skin compared to the healthy control. The increased MCPIP1 mRNA and protein expression level in HS lesions may indicate its possible role in the disease pathogenesis.


2002 ◽  
Vol 98 (4) ◽  
pp. 485-492 ◽  
Author(s):  
Matthew J. Scanlan ◽  
Claudia M. Gordon ◽  
Barbara Williamson ◽  
Sang-Yull Lee ◽  
Yao-Tseng Chen ◽  
...  

2019 ◽  
Vol 33 (1) ◽  
pp. 7-17
Author(s):  
Ximo Mengual ◽  
France Gimnich ◽  
Hannah Petersen ◽  
Jonas J. Astrin

Abstract We examined the effects of different types of specimen labels and tags on pH of different concentrations of ethanol typically used for fluid preservation in natural history collections. Labels were immersed in three different concentrations of ethanol, 96% pure undenatured ethanol (EtOH), 96% EtOH denatured with methyl-ethyl ketone (MEK), and 99.8% pure undenatured EtOH, with or without the presence of insect specimens, and the solutions were evaluated after 26 months for changes over time in pH reading. In general, pH readings of all label trials with 96% and 99.8% ethanol increased over time, except for trials of denatured alcohol, which demonstrated lower pH readings in almost all treatments, regardless of label type. Samples that contained labels with ordinary, nonstandardized, not explicitly acid-free printing paper had higher pH readings compared after the trial. Our observations are a good starting point for further experiments to answer research questions related to chemical interactions with labels in ethanol-preserved specimens, including tissue samples for molecular analyses, which can guide collection staff in their daily work.


2021 ◽  
Author(s):  
Gelena Kakurina ◽  
Olga V Cheremisina ◽  
Elena E Sereda ◽  
Elena S Kolegova ◽  
Irina V Kondakova ◽  
...  

Abstract Purpose: Actin-binding proteins (ABPs) and various signaling systems are involved in the metastasis of squamous cell carcinoma of the larynx and hypopharynx (SCCLH). The clinical significance of these proteins has not yet been determined. We analyzed the relationship between the mRNA level of cofilin 1 (CFL1), profilin 1 (PFN1), adenylyl cyclase-associated protein 1 (CAP1), SNAIL and RND3 with metastasis in the SCCLH tissue. The serum level of the listed ABPs was estimated and the relationship of them with the expression of the corresponding mRNA was carried out. Materials and methods: The expression level of ABPs mRNA was measured by real-time RT-PCR in paired tissue samples taken from 54 patients with SCCLH (T 1-4 N 0-1 M 0 ). Expression analysis was performed using the 2 - ΔΔ CT method. The level of ABPs in the blood serum was measured by ELISA. Statistical analysis was carried out using the SPSS Statistica 20.0 software package. Results: The mRNA expression of the studied genes in tumor tissue of patients with SCCLH T 1-3 N 0 M 0 and T 2-4 N 1-2 M 0 did not differ significantly. High expression of RND3 mRNA was accompanied by an increase in mRNA expression of all studied ABPs. In the blood serum of T 2-4 N 1-2 M 0 patients the level of PFN1 was significantly lower by 21% and the level of CAP1 was higher by 75% compared with the group of patients with T 1-4 N 0 M 0 stage. Conclusion: According to our data RND3 is involved in the regulation of molecular cascades SCCLH metastasis. PFN1 and CAP1 serum level can be a good classifier of metastases in patients with SCCLH.


Sign in / Sign up

Export Citation Format

Share Document