Multi-Omics Analysis Reveals Up-Regulation of APR Signaling, LXR/RXR and FXR/RXR Activation Pathways in Holstein Dairy Cows Exposed to High-Altitude Hypoxia

Abstract

Changes in the environment such as high-altitude hypoxia (HAH) high-altitude hypoxia can lead to adaptive changes in the blood system of mammals. However, there is limited information about the adaptation of Holstein dairy cows introduced to high-altitude areas. This study used 12 multiparous Holstein dairy cows (600 ± 55 kg, average three years old) exposed to HAH conditions in Nyingchi of Tibet (altitude 3000 m) and HAH-free conditions in Shenyang (altitude 50 m). The miRNA microarray analysis and iTRAQ proteomics approach (accepted as more suitable for accurate and comprehensive prediction of miRNA targets) were applied to explore the differences in the plasma proteomic and miRNA profiles in Holstein dairy cows. A total of 70 differential miRNAs (54 up-regulated, Fold change (FC) FC > 2, and 16 down-regulated, FC < 0.5) and 226 differential proteins (132 up-regulated, FC > 1.2, and 94 down-regulated, FC < 0.8) were found in the HAH-stressed group compared with the HAH-free group. Integrative analysis of proteomic and miRNA profiles demonstrated the biological processes associated with differential proteins were the immune response, complement activation, protein activation, and lipid transport. The integrative analysis of canonical pathways were most prominently associated with the APR signaling (z = 1.604), and LXR/RXR activation (z = 0.365), and FXR/RXR activation (z = 0.446) pathways. The current results indicated that Holstein dairy cows exposed to HAH could adapt to high-altitude hypoxia by up-regulating the APR, activating the LXR/RXR and FXE/RXR pathways.

Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish

“…Unlike male, in female three top canonical pathways showed a differentially expressed pattern when compared between acute hypoxia and preconditioning groups with normoxia (AHF vs NF and PHF vs NF). In the present study, since LXR/RXR pathway showed an upregulation in AHF and down regulation in PHF and the activation of LXR/RXR leads to alleviate inflammation (Kong et al, 2019), it is legitimate to state that the neuroprotection in female might come faster by reducing inflammation in PHF eventually. Acetyl-CoA, as a central metabolic intermediate, is widely used in macromolecule biosynthesis and energy production to support cell growth and proliferation (Gao et al, 2016).…”

MicroRNAs as Biomarkers for Animal Health and Welfare in Livestock

“…These events are consistent with chronic stress affecting the physical conditions and increasing the vulnerability of animals to infection and disease. Several studies have investigated the adaptation of cattle managed on pasture in high-altitude regions (86,87). Kong et al investigated the miRNA expression profiles of two breeds of cattle, and found that the levels of circulating miR-155 and miR-17-5p were upregulated in Jersey cows (86), whereas miR-let7a-5p, miR-19a, and miR-181a were upregulated in Holstein cows (87).…”

Dynamic changes in the urine proteome of tumor-bearing mouse models of B16 melanoma and RM-1 prostate cancer

“…In addition to its role as a kinase, FAK is involved in cell proliferation, adhesion, migration, invasion and apoptosis [79][80][81][82]; however, acute response signals, LXR/RXR activation, and FXR/RXR activation were significantly enriched after the tumor was observed. It has been reported that FXR/RXR activation may attempt to reduce inflammation, usually in conjunction with LXR and other receptors, to activate homeostasis in cholesterol and triglyceride metabolism and inhibit inflammation [83].…”

“…Similarly, the pathway analysis showed that the pathways at different time points had their own characteristics, and some of them were reported to be associated with prostate cancer (Table 7). For example, before the tumor was palpable, FXR/RXR activation, LXR/RXR activation [83], mitochondrial dysfunction, acute phase response signaling and other pathways were significantly enriched. It has been reported that the activation of the LXR/RXR and FXR/RXR pathways may alleviate inflammation.…”

“…RXR is a nuclear hormone receptor of the retinoid A receptor family, which is usually used with LXR and FXR receptors. These receptors usually exist in biological and pathological pathways related to glucose, lipid homeostasis and the inflammatory response [83]. The proteomic study of urine in prostate cancer patients with a Gleason score of 6.9 ± 1.1 showed that LXR/RXR is activated and the signal of the acute-phase response is significantly downregulated [84].…”