Genome-Wide Transcriptional Analysis Reveals the Protection against Hypoxia-Induced Oxidative Injury in the Intestine of Tibetans via the Inhibition of GRB2/EGFR/PTPN11 Pathways.
The molecular mechanisms for hypoxic environment causing the injury of intestinal mucosal barrier (IMB) are widely unknown. To address the issue, Han Chinese from 100 m altitude and Tibetans from high altitude (more than 3650 m) were recruited. Histological and transcriptome analyses were performed. The results showed intestinal villi were reduced and appeared irregular, and glandular epithelium was destroyed in the IMB of Tibetans when compared with Han Chinese. Transcriptome analysis revealed 2573 genes with altered expression. The levels of 1137 genes increased and 1436 genes decreased in Tibetans when compared with Han Chinese. Gene ontology (GO) analysis indicated most immunological responses were reduced in the IMB of Tibetans when compared with Han Chinese. Gene microarray showed that there were 25-, 22-, and 18-fold downregulation for growth factor receptor-bound protein 2 (GRB2), epidermal growth factor receptor (EGFR), and tyrosine-protein phosphatase nonreceptor type 11 (PTPN11) in the IMB of Tibetans when compared with Han Chinese. The downregulation of EGFR, GRB2, and PTPN11 will reduce the production of reactive oxygen species and protect against oxidative stress-induced injury for intestine. Thus, the transcriptome analysis showed the protecting functions of IMB patients against hypoxia-induced oxidative injury in the intestine of Tibetans via affecting GRB2/EGFR/PTPN11 pathways.
High Altitude Medical Research Institute, People's Hospital of Tibet Autonomous Region, Lhasa 850000, China; Department of Cardiology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, China.
Kang
0000-0003-1177-3220
K
Li
High Altitude Medical Research Institute, People's Hospital of Tibet Autonomous Region, Lhasa 850000, China; Department of Cardiology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, China.
Luobu
L
Gesang
Department of Gastroenterology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, China.
Zeng
Z
Dan
Department of Cardiology, People's Hospital of Tibet Autonomous Region, Lhasa 850000, China.
Lamu
L
Gusang
D000328:Adult; D015687:Cell Hypoxia / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics; D016000:Cluster Analysis; D015536:Down-Regulation / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D020869:Gene Expression Profiling; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology / Q000648:ultrastructure; D007422:Intestines / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics*; D010455:Peptides / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000235:genetics*; D013194:Staining and Labeling; D018609:Tibet; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D010455:Peptides; D066246:ErbB Receptors; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11