scholarly journals Identification of a miRNA–mRNA Regulatory Networks in Placental Tissue Associated With Tibetan High Altitude Adaptation

2021 ◽  
Vol 12 ◽  
Author(s):  
Noryung Tenzing ◽  
Martha Tissot van Patot ◽  
Huifang Liu ◽  
Qiying Xu ◽  
Juanli Liu ◽  
...  

The Tibetan population has lived and successfully reproduced at high altitude for many generations. Studies have shown that Tibetans have various mechanisms for protection against high-altitude hypoxia, which are probably due, at least in part, to placental adaptation. However, comprehensive in silico analyses of placentas in Tibetans are lacking. We performed a microarray-based comparative transcriptome analysis of 10 Tibetan women from Yushu, Qinghai, CHN (∼3,780 m) and 10 European women living in Leadville, CO, United States (∼3,100 m) for less than three generations. Expression of HIF-1α, STAT3, EGFR, HSP5A, XBP1, and ATF6A mRNA was less in the Tibetan placentas as compared with European placentas. A total of 38 miRNAs were involved in regulating these genes. Differentially expressed genes were enriched for HIF1α signaling pathways, protein processing in the endoplasmic reticulum, PI3K-AKT signaling pathways, and MAPK signaling pathways. Based on the transcriptome profiles, the Tibetan population was distinct from the European population; placental tissues from the Tibetan population are lacking hypoxic responses, and “passivation” occurs in response to hypoxic stress. These results provide insights into the molecular signature of adaptation to high altitudes in these two populations.

2021 ◽  
Vol 12 ◽  
Author(s):  
Yanan Yang ◽  
Haonan Yuan ◽  
Tianliang Yang ◽  
Yongqing Li ◽  
Caixia Gao ◽  
...  

To adapt to a low-oxygen environment, Tibetan pigs have developed a series of unique characteristics and can transport oxygen more effectively; however, the regulation of the associated processes in high-altitude animals remains elusive. We performed mRNA-seq and miRNA-seq, and we constructed coexpression regulatory networks of the lung tissues of Tibetan and Landrace pigs. HBB, AGT, COL1A2, and EPHX1 were identified as major regulators of hypoxia-induced genes that regulate blood pressure and circulation, and they were enriched in pathways related to signal transduction and angiogenesis, such as HIF-1, PI3K-Akt, mTOR, and AMPK. HBB may promote the combination of hemoglobin and oxygen as well as angiogenesis for high-altitude adaptation in Tibetan pigs. The expression of MMP2 showed a similar tendency of alveolar septum thickness among the four groups. These results indicated that MMP2 activity may lead to widening of the alveolar wall and septum, alveolar structure damage, and collapse of alveolar space with remarkable fibrosis. These findings provide a perspective on hypoxia-adaptive genes in the lungs in addition to insights into potential candidate genes in Tibetan pigs for further research in the field of high-altitude adaptation.


2017 ◽  
Vol 1 (Special Issue) ◽  
pp. 113-113
Author(s):  
Nipa Basak ◽  
Sheikh Nizamuddin ◽  
Kumarasamy Thangaraj

ExRNA ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
P. Khurana ◽  
A. Gupta ◽  
R. Sugadev ◽  
Y. K. Sharma ◽  
R. Varshney ◽  
...  

Abstract Background Given the worldwide spread of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (nSARS-CoV-2) infection pandemic situation, research to repurpose drugs, identify novel drug targets, vaccine candidates have created a new race to curb the disease. While the molecular signature of nSARS-CoV-2 is still under investigation, growing literature shows similarity among nSARS-CoV-2, pulmonary edema, and thromboembolic disorders due to common symptomatic features. A network medicine approach is used to to explore the molecular complexity of the disease and to uncover common molecular trajectories of edema and thrombosis with nSARS-CoV-2. Results and conclusion A comprehensive nSARS-CoV-2 responsive miRNA: Transcription Factor (TF): gene co-regulatory network was built using host-responsive miRNAs and it’s associated tripartite, Feed-Forward Loops (FFLs) regulatory circuits were identified. These regulatory circuits regulate signaling pathways like virus endocytosis, viral replication, inflammatory response, pulmonary vascularization, cell cycle control, virus spike protein stabilization, antigen presentation, etc. A unique miRNA-gene regulatory circuit containing a consortium of four hub FFL motifs is proposed to regulate the virus-endocytosis and antigen-presentation signaling pathways. These regulatory circuits also suggest potential correlations/similarity in the molecular mechanisms during nSARS-CoV-2 infection, pulmonary diseases and thromboembolic disorders and thus could pave way for repurposing of drugs. Some important miRNAs and genes have also been proposed as potential candidate markers. A detailed molecular snapshot of TGF signaling as the common pathway, that could play an important role in controlling common pathophysiologies among diseases, is also put forth.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xing Fu ◽  
Chunyan Yang ◽  
Bing Chen ◽  
Kexing Zeng ◽  
Siyuan Chen ◽  
...  

Abstract Background Chinese Yunnan Province, located in the Yunnan–Guizhou Plateau, is a famous tourist paradise where acute high-altitude illness common occurs among lowland people visitors due to non-acclimatization to the acute hypobaric hypoxia (AHH) conditions. Traditional Chinese medicine, such as Qi-Long-Tian (QLT) formula, has shown effectiveness and safety in the treatment of acute high-altitude diseases. The aim of this study was to clarify the therapeutic mechanisms of this traditional formula using a rat model in a simulated plateau environment. Methods Following testing, lung tissue samples were evaluated by hematoxylin–eosin staining and for biochemical characteristics. mRNA-Seq was used to compare differentially expressed genes in control rats, and in rats exposed to AHH and AHH with QLT treatment. Results Inflammation-related effectors induced following QLT treatment for AHH included MMP9 and TIMP1, and involved several phosphorylation signaling pathways implicated in AHH pathogenesis such as PI3K/AKT and MAPK signaling. Conclusion This study provides insights into the major signaling pathways induced by AHH and in the protective mechanisms involved in QLT formula activity.


Insects ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 631
Author(s):  
Yanjie Liu ◽  
Huiyue Zhao ◽  
Qihua Luo ◽  
Yadong Yang ◽  
Guangshuo Zhang ◽  
...  

Bombus pyrosoma is one of the most abundant bumblebee species in China, with a distribution range of very varied geomorphology and vegetation, which makes it an ideal pollinator species for research into high-altitude adaptation. Here, we sequenced and assembled transcriptomes of B. pyrosoma from the low-altitude North China Plain and the high-altitude Tibet Plateau. Subsequent comparative analysis of de novo transcriptomes from the high- and low-altitude groups identified 675 common upregulated genes (DEGs) in the high-altitude B. pyrosoma. These genes were enriched in metabolic pathways and corresponded to enzyme activities involved in energy metabolism. Furthermore, according to joint analysis with comparative metabolomics, we suggest that the metabolism of coenzyme A (CoA) and the metabolism and transport of energy resources contribute to the adaptation of high-altitude B. pyrosoma. Meanwhile, we found many common upregulated genes enriched in the Toll and immune deficiency (Imd)signaling pathways that act as important immune defenses in insects, and hypoxia and cold temperatures could induce the upregulation of immune genes in insects. Therefore, we suppose that the Toll and Imd signaling pathways also participated in the high-altitude adaptation of B. pyrosoma. Like other organisms, we suggest that the high-altitude adaptation of B. pyrosoma is controlled by diverse mechanisms.


Author(s):  
Jay F. Storz ◽  
Zachary A. Cheviron

Population genomic studies of humans and other animals at high altitude have generated many hypotheses about the genes and pathways that may have contributed to hypoxia adaptation. Future advances require experimental tests of such hypotheses to identify causal mechanisms. Studies to date illustrate the challenge of moving from lists of candidate genes to the identification of phenotypic targets of selection, as it can be difficult to determine whether observed genotype–phenotype associations reflect causal effects or secondary consequences of changes in other traits that are linked via homeostatic regulation. Recent work on high-altitude models such as deer mice has revealed both plastic and evolved changes in respiratory, cardiovascular, and metabolic traits that contribute to aerobic performance capacity in hypoxia, and analyses of tissue-specific transcriptomes have identified changes in regulatory networks that mediate adaptive changes in physiological phenotype. Here we synthesize recent results and discuss lessons learned from studies of high-altitude adaptation that lie at the intersection of genomics and physiology. Expected final online publication date for the Annual Review of Animal Biosciences, Volume 9 is February 16, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


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