The Expression Regulatory Network in the Lung Tissue of Tibetan Pigs Provides Insight Into Hypoxia-Sensitive Pathways in High-Altitude Hypoxia.

Yanan Yang,Caixia Gao,Yongqing Li,Tianliang Yang,Shengguo Zhao,Haonan Yuan,Ting Jiao,Yuan Cai

doi:10.3389/fgene.2021.691592

Abstract

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.

Highlights

Tibetans are a unique and geographically isolated pig breed that inhabits the Qinghai-Tibet Plateau, which has an extreme environment with high altitudes (Wang et al, 2018; Ma et al, 2019)
The sections from the Tibetan male piglets from the highlands (TH) group were characterized by smooth muscle hyperplasia and larger alveoli, while those from the Landrace male piglets migrated to the highlands (LH) group were characterized by a thicker alveolar septum
The results indicated that 71.09, 17.00, and 11.90% of the genes were enriched in the biological process (BP), cell component (CC), and molecular function (MF) categories, respectively, in the TH-vs.Tibetan male piglets migrated to the lowlands (TL) comparison (p < 0.05)

Summary

Introduction

Tibetans are a unique and geographically isolated pig breed that inhabits the Qinghai-Tibet Plateau, which has an extreme environment with high altitudes (Wang et al, 2018; Ma et al, 2019). This unique ecological condition is characterized by low air pressure, reduced oxygen content, and high ultraviolet radiation, imposing extreme physiological challenges on domestic animals, and failure to adapt will lead to altitude illness or even death (Cao et al, 2017; Lancuo et al, 2019; Qi et al, 2019). The hypoxia-inducible factor-1 (HIF-1), vascular endothelial growth factor (VEGF), and mitogen-activated protein kinase (MAPK) signaling pathways are typical hypoxia-associated pathways (Lee et al, 2016; Zhang et al, 2018; Nicolas et al, 2019), and some mRNAs (PHD2, VHL, and FIH-1) and miRNAs (miR-363, miR421, and miR-204) have been implicated in the regulation of the HIF-1 signaling pathway (Semenza, 2007; Ge et al, 2016; Wang et al, 2016; Xie et al, 2016)

Methods

Results

Discussion

Conclusion