Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury

Li, Kang; Gesang, Luobu; Zhang, Dan; Gusang, Lamu; Dawa, Ciren; Nie, Yongzhan

doi:10.1371/journal.pone.0140534

Cited by 7 publications

(7 citation statements)

References 26 publications

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“…Comparing with our reported work [26, 33], the population size was increased from 6 and 24 to 45 subjects in the present study. Furthermore, the color of brown lesions under the mucosa in upper gastrointestinal tract was much darker than before reported in HAPC patients (Figure 1).…”

Section: Discussionsupporting

confidence: 56%

Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Cai

2019

BioMed Research International

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Background. Living at a high plateau in a very hostile environment and low oxygen levels often leads to the development of high-altitude polycythemia (HAPC) and gastric mucosal lesions caused by high-level reactive oxygen species (ROS). Hypoxia-inducible factor-1A (HIF-1A) helps maintain oxygen homeostasis by promoting the transcription of various genes and can be affected by ROS levels. To evaluate the molecular mechanism by which HAPC causes the gastric mucosal lesions, the expression of HIF-1A was measured in Tibetans with HAPC and in healthy subjects. Ultrastructural, histopathological, and immunohistochemical analyses were performed in the gastric tissues of both groups, and the expression of HIF-1A in the gastric mucosa was detected using qPCR and Western Blot. Results. The microvessel density and average diameter of gastric mucosal vessels were significantly greater in the HAPC patients than in the healthy subjects (p < 0.05). The number of red blood cells in the gastric mucosa was also significantly higher in the HAPC group than in the healthy subjects (p < 0.05). In addition, the density of the mitochondrial vacuoles and endoplasmic reticulum and pathological apoptosis were significantly increased in the gastric cells from HAPC patients compared to those from the healthy subjects. The levels of ROS and HIF-1A in the gastric mucosa were increased in HAPC patients compared to those in controls (p < 0.05). Conclusions. An increased level of HIF-1A was associated with HAPC development in the stomach of Tibetans living at a high altitude. ROS upregulated the levels of HIF-1A. Thus, ROS-mediated HIF-1A signaling transduction may be the mechanism associated with HAPC-induced gastric lesions.

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Section: Discussionsupporting

confidence: 56%

Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Cai

2019

BioMed Research International

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“…Consequently, cis-eQTLs associated with the APOA4 and APOC3 gene expression may be associated with the PTB risk. In humans, genetic variants in the APOA1 -APOC3-APOA4 cluster has been associated with the risk of Alzheimer disease, polycythemia induced gastric injury, and metabolic syndrome [42][43][44] . However, we did not find any association between the cis-eQTLs regulating APOA4 and APOC3 gene expression and PTB risk in our case-control study.…”

Section: Discussionmentioning

confidence: 99%

Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression

Canive

Fernández-Jiménez

Casáis

et al. 2021

Sci Rep

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Although genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with the susceptibility to Mycobacterium avium subsp. paratuberculosis (MAP) infection, only a few functional mutations for bovine paratuberculosis (PTB) have been characterized. Expression quantitative trait loci (eQTLs) are genetic variants typically located in gene regulatory regions that alter gene expression in an allele-specific manner. eQTLs can be considered as functional links between genomic variants, gene expression, and ultimately phenotype. In the current study, peripheral blood (PB) and ileocecal valve (ICV) gene expression was quantified by RNA-Seq from fourteen Holstein cattle with no lesions and with PTB-associated histopathological lesions in gut tissues. Genotypes were generated from the Illumina LD EuroG10K BeadChip. The associations between gene expression levels (normalized read counts) and genetic variants were analyzed by a linear regression analysis using R Matrix eQTL 2.2. This approach allowed the identification of 192 and 48 cis-eQTLs associated with the expression of 145 and 43 genes in the PB and ICV samples, respectively. To investigate potential relationships between these cis-eQTLs and MAP infection, a case–control study was performed using the genotypes for all the identified cis-eQTLs and phenotypical data (histopathology, ELISA for MAP-antibodies detection, tissue PCR, and bacteriological culture) of 986 culled cows. Our results suggested that the heterozygous genotype in the cis-eQTL-rs43744169 (T/C) was associated with the up-regulation of the MDS1 and EVI1 complex (MECOM) expression, with positive ELISA, PCR, and bacteriological culture results, and with increased risk of progression to clinical PTB. As supporting evidence, the presence of the minor allele was associated with higher MECOM levels in plasma samples from infected cows and with increased MAP survival in an ex-vivo macrophage killing assay. Moreover, the presence of the two minor alleles in the cis-eQTL-rs110345285 (C/C) was associated with the dysregulation of the eukaryotic elongation factor 1-α2 (eEF1A2) expression and with increased ELISA (OD) values. Finally, the presence of the minor allele in the cis-eQTL rs109859270 (C/T) was associated with the up-regulation of the U1 spliceosomal RNA expression and with an increased risk of progression to clinical PTB. The introduction of these novel functional variants into marker-assisted breeding programs is expected to have a relevant effect on PTB control.

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“…Syam et al (9) demonstrated that hypoxia leads to more severe gastric ulceration using a systemic hypoxia rat model. Though we have found some genes differentially expressed in HAPC-induced GML, the understanding of the underlying molecular mechanisms is currently limited (10).…”

Section: Introductionmentioning

confidence: 89%

Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia

Li¹,

Gesang²,

Cai³

2017

Experimental and Therapeutic Medicine

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Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury

Cited by 7 publications

References 26 publications

Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Gastric Mucosal Lesions in Tibetans with High-Altitude Polycythemia Show Increased HIF-1A Expression and ROS Production

Identification of loci associated with susceptibility to bovine paratuberculosis and with the dysregulation of the MECOM, eEF1A2, and U1 spliceosomal RNA expression

Mechanism of apoptosis involved in gastric mucosal lesions in Tibetans with high-altitude polycythemia

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