Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy

Lili E Fodor,András Gézsi,Ildikó Ungvári,Ágnes F. Semsei,Zsófia Gál,Adrienne Nagy,Gabriella Gálffy,Lilla Tamási,András Kiss,Péter Antal,Csaba Szalai 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.3

Purpose: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes. Methods: The levels of gene expressions of the members of the Hippo/YAP1 were compared. The presence of the proteins of the YAP1 and FRMD6 were analyzed with Western blot in induced sputum of 18 asthmatic subjects and 10 control subjects. Fourteen single nucleotide polymorphisms (SNPs) in the YAP1 gene were genotyped in 522 asthmatic subjects and 711 healthy controls. The results were evaluated with traditional frequentist methods and with Bayesian network-based Bayesian multilevel analysis of relevance (BN-BMLA). Results: The mRNA of all the members of the Hippo/YAP1 pathway could be detected in the induced sputum of both controls and cases. A correlation was found between YAP1 mRNA levels and sputum bronchial epithelial cells (r=0.575, P=0.003). The signal for the FRMD6 protein could be detected in all sputum samples while the YAP1 protein could not be detected in the sputum samples, of the healthy controls and severe asthmatics, but it was detectable in mild asthmatics. The rs2846836 SNP of the YAP1 gene was significantly associated with exercise-induced asthma (odds ratio [OR]=2.1 [1.3-3.4]; P=0.004). The distribution of genotypes of rs11225138 and certain haplotypes of the YAP1 gene showed significant differences between different asthma severity statuses. With BN-BMLA, 2 SNPs, genetic variations in the FRMD6 gene proved to be the most relevant to exercise-induced asthma and allergic rhinitis. These 2 SNPs through allergic rhinitis and exercise-induced asthma were in epistatic interaction with each other. Conclusions: Our results provided additional evidence that the FRMD6/Hippo/YAP1 pathway plays a role in the pathogenesis of asthma. If additional studies can confirm these findings, this pathway can be a potential novel therapeutic target in asthma and other inflammatory airway diseases.

Genetic Diversity of Natural and Artificial Populations of Model Grass Brachypodium Species Evaluated by AFLP Markers

Zhang, Lili,Jeon, Young-Ju,Kang, Si-Yong,Lee, Geung-Joo 한국원예학회 2012 Horticulture, Environment, and Biotechnology Vol.53 No.2

Brachypodium, a monocot grass with wide distribution in temperate areas, has been considered a new model plant for many grass species, such as turfgrass or miscanthus, due to its small genome size, self-pollination, rapid life cycle, higher seed yield, and small stature. The objectives of this study were to compare the genetic diversity of natural and artificial populations, and to determine the effects of ${\gamma}$-radiation on genetic variability when evaluated by amplified fragment length polymorphism (AFLP) markers. Two populations used in this study include 66 plant introductions (PI) from the U.S. Department of Agriculture (USDA; POP1), and 43 mutants derived from one of the plant introductions, Bd43 (PI 227011; POP2) treated with a ${\gamma}$-irradiation ranging from 100 to 600 Gy. The highest performance of the phenotypic traits was observed at 200 Gy for germination rate, 100 Gy for height, and 600 Gy for tiller number, implying that the $LD_{50}$ for determining of optimum dosage depends on the physiological parameters measured. Based on AFLP analysis, POP2 showed higher polymorphism (79.4%), PIC (polymorphism information content; 0.162), and genetic diversity (0.195) than POP1 (59.4%, 0.113, and 0.130, respectively). Those three genetic parameters were evaluated for the mutants derived at various ${\gamma}$-radiation dosages and were found to be the highest when irradiated at 300 Gy. Artificial mutagenesis using ${\gamma}$-radiation improved genetic diversity compared to that of the natural population, and 300 Gy was a useful dosage to enlarge genetic variability in Brachypodium. Results suggest that a dosage maximizing the genetic diversity when evaluated with AFLP markers is an alternative index to $LD_{50}$ for determining the optimum level for mutation induction.

Metabolic responses and arginine kinase expression of juvenile cuttlefish (<i>Sepia pharaonis</i>) under salinity stress

Yin, Shang-Jun,Zhang, Linmeng,Zhang, Lili,Wan, Jiaxin,Song, Wei,Jiang, Xiamin,Park, Yong-Doo,Si, Yue-Xiu Elsevier 2018 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.113 No.-

<P><B>Abstract</B></P> <P>The pharaoh cuttlefish <I>Sepia pharaonis</I> is particularly sensitive to environmental changes in its breeding environment. The breeding of <I>S</I>. <I>pharaonis</I> larvae was carried out in different salinities for 48h, and the changes in survival rate, histological structure, energy metabolism, and anti-oxidative stress parameters were investigated and correlated with arginine kinase (AK) expression changes in muscle and liver tissues. The suitable salinity for larvae cultivation ranged from 24 to 30‰, and the survival rate showed a significant decline at 21‰ salinity. Histological observations of muscle and liver showed that changes in salinity and osmotic pressure had an adverse effect on tissue structure. Measurements of glycogen and lactic acid levels suggested that <I>S</I>. <I>pharaonis</I> could dynamically adjust energy metabolism to provide additional energy under unsuitable salinity. The protein levels and enzyme activities of AK in muscle significantly increased at 21‰ salinity. The results were consistent with prompt replenishment of phosphoarginine stores during salinity stress to maintain a dynamic ATP balance, suggesting that AK plays an important role in the regulation of energy metabolism. This study provides insight into metabolic changes during salinity stress and sheds light on the functional role of AK in <I>S</I>. <I>pharaonis</I>.</P>

tae-miR9674a, a microRNA member of wheat, confers plant drought and salt tolerance through modulating the stomata movement and ROS homeostasis

Wang Ling,Bai Xinyang,Qiao Yuanjinzi,Si Lili,Yu Zidi,Ni Chenyang,Li Tianjiao,Guo Chengjin,Xiao Kai 한국식물생명공학회 2023 Plant biotechnology reports Vol.17 No.4

The members of the microRNA (miRNA) family exert essential roles in modulating plant growth and development as well as responses to diverse stresses, through negatively regulating their target genes at posttranscriptional or translational levels. In this study, we characterized taemiR9674a, a miRNA member in T. aestivum, in mediating plant responses to drought and salt stresses. Seven genes in total were predicted to act as the targets of tae-miR9674a via modulation of transcript cleavage. The transcripts of tae-miR9674a in roots and leaves were response to both stresses of drought and salt, displaying to be gradually upregulated following the progression of a 27-h regime of above stress treatments. The transgenic tobacco lines of tae-miR9674a exhibited modified growth traits under drought and salt treatments. Of these, the line with miRNA overexpression (i.e., Sen 1) improved drastically on plant biomass, leaf area, and root length, whereas that with its knockdown expression (Anti 1) significantly alleviated on above growth traits compared with wild type. The modified stress responses of tae-miR9674a were shown to be closely associated with the role of miRNA in regulating a suite of physiological parameters, of which Sen 1 displayed improved osmotic stress defensive-related traits, such as fastened stomata closing rate, increased leaf water retention capacity, enhanced osmolytes contents, and elevated antioxidant enzyme (AE) activities. The expression of NtP5CS1 involving proline biosynthesis and NtFeSOD, NtCAT1 and NtPOD4, the AE genes involved in modulating ROS homeostasis, was upregulated in Sen 1 upon drought and salt stresses, suggesting their involvement in miRNA-mediated plant drought and salt responses. Transcriptome analysis indicated that tae-miR9674a leads to modified expression of quantities of genes that functionally associate with GO terms “biological process”, “cellular component”, and “molecular function”, which are overrepresented by the biochemical pathways of phytohormones (i.e., ethylene and jasmonic acid), salt response, salt/drought osmotic stress response through abscisic acid-dependent pathway and reactive oxygen species (ROS) homeostasis. Our investigation suggested that tae-miR9674a is an essential mediator in plant osmotic stress tolerance by positively regulating osmotic stress acclimation, cellular ROS homeostasis, and related defensive processes.

Novel genes in Human Asthma Based on a Mouse Model of Allergic Airway Inflammation and Human Investigations

Gergely Temesi,Viktor Virág,Éva Hadadi,Ildikó Ungvári,Lili E Fodor,András Bikov,Adrienne Nagy,Gabriella Gálffy,Lilla Tamási,Ildikó Horváth,András Kiss,Gábor Hullám,András Gézsi,Péter Sárközy,Péter Ant 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.6

Purpose:Based on a previous gene expression study in a mouse model of asthma, we selected 60 candidate genes and investigated their possible roles in human asthma. Methods: In these candidate genes, 90 SNPs were genotyped using MassARRAY technology from 311 asthmatic children and 360 healthy controls of the Hungarian (Caucasian) population. Moreover, gene expression levels were measured by RT PCR in the induced sputum of 13 asthmatics and 10 control individuals. t-tests, chi-square tests, and logistic regression were carried out in order to assess associations of SNP frequency and expression level with asthma. Permutation tests were performed to account for multiple hypothesis testing. Results: The frequency of 4 SNPs in 2 genes differed significantly between asthmatic and control subjects: SNPs rs2240572, rs2240571, rs3735222 in gene SCIN, and rs32588 in gene PPARGC1B. Carriers of the minor alleles had reduced risk of asthma with an odds ratio of 0.64 (0.51-0.80; P=7×10-5) in SCIN and 0.56 (0.42-0.76; P=1.2×10-4) in PPARGC1B. The expression levels of SCIN, PPARGC1B and ITLN1 genes were significantly lower in the sputum of asthmatics. Conclusions: Three potentially novel asthma-associated genes were identified based on mouse experiments and human studies.