scholarly journals KLF4, a Key Regulator of a Transitive Triplet, Acts on the TGF-β Signaling Pathway and Contributes to High-Altitude Adaptation of Tibetan Pigs

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Wang ◽  
Yuanyuan Guo ◽  
Shengwei Liu ◽  
Chaoxin Zhang ◽  
Tongyan Cui ◽  
...  
Keyword(s):  
Network Analysis ◽  
High Altitude ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Large Scale ◽  
Mammalian Species ◽  
Hypoxia Tolerance ◽  
Genetic Mechanism ◽  
The Tibetan Plateau ◽  
Tibetan Pigs

Tibetan pigs are native mammalian species on the Tibetan Plateau that have evolved distinct physiological traits that allow them to tolerate high-altitude hypoxic environments. However, the genetic mechanism underlying this adaptation remains elusive. Here, based on multitissue transcriptional data from high-altitude Tibetan pigs and low-altitude Rongchang pigs, we performed a weighted correlation network analysis (WGCNA) and identified key modules related to these tissues. Complex network analysis and bioinformatics analysis were integrated to identify key genes and three-node network motifs. We found that among the six tissues (muscle, liver, heart, spleen, kidneys, and lungs), lung tissue may be the key organs for Tibetan pigs to adapt to hypoxic environment. In the lung tissue of Tibetan pigs, we identified KLF4, BCL6B, EGR1, EPAS1, SMAD6, SMAD7, KDR, ATOH8, and CCN1 genes as potential regulators of hypoxia adaption. We found that KLF4 and EGR1 genes might simultaneously regulate the BCL6B gene, forming a KLF4–EGR1–BCL6B complex. This complex, dominated by KLF4, may enhance the hypoxia tolerance of Tibetan pigs by mediating the TGF-β signaling pathway. The complex may also affect the PI3K-Akt signaling pathway, which plays an important role in angiogenesis caused by hypoxia. Therefore, we postulate that the KLF4–EGR1–BCL6B complex may be beneficial for Tibetan pigs to survive better in the hypoxia environments. Although further molecular experiments and independent large-scale studies are needed to verify our findings, these findings may provide new details of the regulatory architecture of hypoxia-adaptive genes and are valuable for understanding the genetic mechanism of hypoxic adaptation in mammals.

KLF4, a Key Regulator of a Transitive Triplet, Acts on the TGF-β Signaling Pathway and Contributes to High-Altitude Adaptation of Tibetan Pigs

2020 ◽  
Author(s):  
Tao Wang ◽  
Yuanyuan Guo ◽  
Shengwei Liu ◽  
Chaoxin Zhang ◽  
Tongyan Cui ◽  
...  
Keyword(s):  
Network Analysis ◽  
High Altitude ◽  
Signaling Pathway ◽  
Mammalian Species ◽  
The Tibetan Plateau ◽  
Tibetan Pigs ◽  
Regulatory Architecture ◽  
Hypoxia Adaptation ◽  
Suitable Animal Model ◽  
Transcriptional Changes

Abstract Background: Tibetan pigs are native mammalian species on the Tibetan Plateau that have evolved distinct physiological traits that allow them to tolerate high-altitude hypoxic environments. They can be used as a suitable animal model for exploring the molecular mechanism of hypoxia adaptation in high-altitude organisms.Results: Here, based on multi-tissue transcriptional data from high-altitude Tibetan pigs and low-altitude Rongchang pigs, we performed a weighted correlation network analysis (WGCNA) and identified key modules related to these tissues. Complex network analysis and bioinformatics analysis were integrated to identify key genes and size-3 network motifs. The results showed that compared to other tissues, the lungs of Tibetan pigs and Rongchang pigs are more significantly different, showing more adaptive transcriptional changes. In the lung tissues of Tibetan pigs, we identified KLF4, BCL6B, EGR1, EPAS1, SMAD6, SMAD7, KDR, ATOH8 and CCN1 genes as potential regulators of hypoxia adaption. We found that KLF4 and EGR1 genes simultaneously regulate the BCL6B gene, forming a KLF4-EGR1-BCL6B transitive triplet. This transitive triplet, dominated by KLF4, may enhance the hypoxia adaptability of Tibetan pigs by mediating the TGF-β signaling pathway. This triplet also regulates the KDR gene, which is involved in the PI3K-Akt signaling pathway and plays an important role in hypoxia adaptation. Conclusions: We postulate that the KLF4-EGR1-BCL6B transitive triplet may contribute to the adaptation of Tibetan pigs to hypoxic environments. These findings provide new details of the regulatory architecture of hypoxia-adaptive genes and are valuable for understanding the genetic mechanism of hypoxic adaptation in mammals.

Resource selection in a high-altitude rangeland equid, the kiang (Equus kiang): influence of forage abundance and quality at multiple spatial scales

2014 ◽  
Vol 92 (3) ◽  
pp. 239-249 ◽  
Author(s):  
Antoine St-Louis ◽  
Steeve D. Côté
Keyword(s):  
High Altitude ◽  
Resource Selection ◽  
Large Scale ◽  
Plant Biomass ◽  
Spatial Scales ◽  
Plant Quality ◽  
The Tibetan Plateau ◽  
Higher Plant ◽  
Feeding Site ◽  
Spatial And Temporal Scales

Herbivores foraging in arid and seasonal environments often face choices between plant patches varying in abundance and nutritional quality at several spatial and temporal scales. Because of their noncompartmented digestive system, equids typically rely on abundant forage to meet their nutrient requirements. In forage-limited environments, therefore, scarcity of food resources represents a challenge for wild equids. We investigated hierarchical resource-selection patterns of kiangs (Equus kiang Moorcroft, 1841), a wild equid inhabiting the high-altitude steppes of the Tibetan Plateau, hypothesizing that vegetation abundance would be the main factor driving resource selection at a large scale and that plant quality would influence resource selection at finer scales. We investigated resource-selection patterns at three spatial levels (habitat, feeding site, and plant (vegetation groups, i.e., grasses, sedges, forbs, and shrubs)) during summer and fall. At the habitat level, kiangs selected both mesic and xeric habitats in summer and only xeric habitats (plains) during fall. At the feeding-site level, feeding sites had higher plant biomass and percentage of green foliage than random sites in the same habitats. At the plant level, grasses were selected over forbs and shrubs, and sedges were used in proportion to their availability during all seasons. Our results indicate that resource-selection patterns in kiangs vary across scales and that both forage abundance and quality play a role in resource selection. Plant quality appeared more important than hypothesized, possibly to increase daily nutrient intake in forage-limited and highly seasonal high-altitude rangelands.

scholarly journals Network Biology led identification of critical miRNA modules for High Altitude hypoxia and their potential as dietary supplements

2021 ◽  
Author(s):  
Apoorv Gupta ◽  
Sugadev R ◽  
Y K Sharma ◽  
Pankaj Khurana
Keyword(s):  
Network Analysis ◽  
High Altitude ◽  
Regulatory Networks ◽  
Sequence Similarity ◽  
Functional Module ◽  
Mammalian Species ◽  
Differentially Expressed ◽  
Mammalian Host ◽  
High Altitudes ◽  
Tf Gene

Abstract Early ascent to high altitude can cause severe damage to body functions and may lead to many fatal high-altitude disorders. To cope up with such conditions, the human body undergoes physiological and biochemical changes in order to adapt to extreme environmental conditions at high altitudes. Several microRNAs (miRNAs), Transcription Factors (TFs), and genes have been studied separately for their role in early adaptive molecular responses. We hypothesize that network analysis of miRNA-TF-gene co-regulatory networks of circulatory miRNAs (CmiRNAs) which are differentially expressed at high altitudes could reveal a complex regulatory functional module that might be controlling molecular adaptive responses at high altitude. A comprehensive and non-redundant list of differentially expressed human CmiRNAs during high altitude ascent was collated and 470 Feed-Forward Loops (FFLs) tripartite motifs were identified in the miRNA-TF-gene co-regulatory networks. Network analysis and K-means clustering identified 11 biologically overrepresented FFLs regulated by 8 miRNAs hsa-miR-335-5p, hsa-miR-26a-1-3p, hsa-miR-210-3p, hsa-miR-193b-3p, hsa-miR-17-5p, hsa-miR-16-5p, hsa-miR-5582-5p and hsa-miR-130a-3p. Pathway enrichment identified metabolism and inflammation as important hallmark responses responsible for high altitude adaptation. These miRNAs were evaluated for their supplementation from dietary sources. Phylogenetic analysis with 4 other mammalian and non-mammalian species showed that Bos taurus (cattle) milk could be a possible source of these dietary miRNAs. Exogenous miRNAs bta-mir-16-1, bta-mir-130a, bta-miR-335, and bta-miR-210 have >95% of sequence similarity and could become potential dietary miRNAs candidates. The sequence, structural properties, and high AGO2 binding efficiency of all these exogenous miRNAs show good serum stability and cellular uptake possibility in the mammalian host. Bta-miR-210 with highest Minimal Folding free Energy Index (MFEI) and highest Atomic Contact Energy (ACE) with AGO2 has the best potential to be a dietary supplement.

Large-Scale Network Analysis for Online Social Brand Advertising

MIS Quarterly ◽  
2016 ◽  
Vol 40 (4) ◽  
pp. 849-868 ◽  
Author(s):  
Kunpeng Zhang ◽  
◽  
Siddhartha Bhattacharyya ◽  
Sudha Ram ◽  
◽  
...  
Keyword(s):  
Network Analysis ◽  
Large Scale ◽  
Large Scale Network ◽  
Brand Advertising ◽  
Scale Network

Molecular mechanism of TLR4 mediated T cell immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway

2020 ◽  
Vol 13 ◽  
Author(s):  
Kun Xiao ◽  
Fei Zhao ◽  
WenJie Xie ◽  
Jian Ding ◽  
XiaoAn Gong ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Lung Tissue ◽  
Acute Injury ◽  
Tissue Homogenate ◽  
Control Group ◽  
Pathological Features ◽  
Mhc I ◽  
Immune Effect

Objective: To explore and investigate the molecular mechanism of TLR4 mediated T cell immune effect in transfusion-induced acute injury based on SLIT2/ROBO4 signaling pathway. Methods: Sixty C57/BL6 male mice (Wild type, WT) aged 8 to 10 weeks were randomly divided into 5 groups: 1) normal type WT, 2) LPS control group of WT type lipopolysaccharide, 3) WT type TRALI group (LPS + MHC-I mAb), 4) (TLR4 antibody) lipopolysaccharide LPS control group, 5) (TLR4 antibody) TRALI group (LPS + MHC-I mAb). Mice were dosed with LPS (0.1 mg / kg), and MHC-I mAb (2 mg / kg) was injected into the tail vein 24 hours later for modeling. After 2 hours, mice were sacrificed and experimental samples were collected. HE staining was performed to detect pathological features. The myeloperoxidase (MPO) activity and the level of IL-2, IL-6, TNF, IFN-γ, IL-17A as well as IL-10 were measured in the lung tissue homogenate supernatant. Blood, spleen single cell suspension and bronchoalveolar lavage fluid (BALF) were collected to detect the ratio of Treg and Th17 cells by flow cytometry, respectively. RT-PCR and WB indicated the mRNA or protein expression of CDH5 (Cadherin-5), SLIT2 and ROBO4 in mouse lung tissue and pulmonary vascular tissue respectively. Results: TLR4 mAb treatment decreases the pathological features of LPS induced ALI model in vivo. And so does the MPO activity as well as the level of proinflammatory factors in the lung tissue. TLR4 exerts its function through the changes of Treg/Th17 ratio via SLIT2/ROBO4 signaling pathway and downregulating CDH5 and SETSIP in ALI model. Conclusion: TLR4 mediates immune response in LPS induced ALI model through SLIT2/ROBO4 signaling pathway.

scholarly journals Identification of a juvenile-hormone signaling inhibitor via high-throughput screening of a chemical library

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Takumi Kayukawa ◽  
Kenjiro Furuta ◽  
Keisuke Nagamine ◽  
Tetsuro Shinoda ◽  
Kiyoaki Yonesu ◽  
...  
Keyword(s):  
Juvenile Hormone ◽  
Cell Line ◽  
Signaling Pathway ◽  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Ex Vivo ◽  
Agricultural Field ◽  
Chemical Library ◽  
Field Development

Abstract Insecticide resistance has recently become a serious problem in the agricultural field. Development of insecticides with new mechanisms of action is essential to overcome this limitation. Juvenile hormone (JH) is an insect-specific hormone that plays key roles in maintaining the larval stage of insects. Hence, JH signaling pathway is considered a suitable target in the development of novel insecticides; however, only a few JH signaling inhibitors (JHSIs) have been reported, and no practical JHSIs have been developed. Here, we established a high-throughput screening (HTS) system for exploration of novel JHSIs using a Bombyx mori cell line (BmN_JF&AR cells) and carried out a large-scale screening in this cell line using a chemical library. The four-step HTS yielded 69 compounds as candidate JHSIs. Topical application of JHSI48 to B. mori larvae caused precocious metamorphosis. In ex vivo culture of the epidermis, JHSI48 suppressed the expression of the Krüppel homolog 1 gene, which is directly activated by JH-liganded receptor. Moreover, JHSI48 caused a parallel rightward shift in the JH response curve, suggesting that JHSI48 possesses a competitive antagonist-like activity. Thus, large-scale HTS using chemical libraries may have applications in development of future insecticides targeting the JH signaling pathway.

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