Identification of potential target genes and related regulatory transcription factors in spontaneous hairline fracture induced by hypervitaminosis A.

Abstract

BACKGROUND:

The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture.

METHODS:

The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken. Based on the MSigDB database, the potential regulatory transcription factors (TFs) were identified.

RESULTS:

A total of 373 DEGs including 342 up- and 31 down-regulated genes were identified. These DEGs were significantly enriched in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism. Finally, the most significant regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2 (NRF2) and ELK1, Member of ETS Oncogene Family (ELK1).

CONCLUSION:

Key TFs including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1, Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our findings will provide new insights for the target selection in clinical application to prevent spontaneous fracture induced by hypervitaminosis A.

• Authors: Chuangang Peng, Qi Yang, Bo Wei, Yong Liu, Yuxiang Li, Dawei Gu, Guochao Yin, Bo Wang, Dehui Xu, Xuebing Zhang, Daliang Kong
• Journal: Injury (Injury) Vol. 48 Issue 7 Pg. 1475-1479 (Jul 2017) ISSN: 1879-0267 [Electronic] Netherlands
• PMID: 28511966 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

• E2f1 protein, rat
• E2F1 Transcription Factor
• Elk1 protein, rat
• ets-Domain Protein Elk-1
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Transcription Factors
• Vitamin A

Topics

• Animals
• Male
• Rats
• Bone Marrow Cells (drug effects, metabolism)
• Cortical Bone (drug effects, metabolism)
• E2F1 Transcription Factor (metabolism)
• Endoplasmic Reticulum (metabolism)
• Endoplasmic Reticulum Stress
• ets-Domain Protein Elk-1 (metabolism)
• Fractures, Spontaneous (etiology, genetics)
• Gene Expression Regulation (drug effects, genetics)
• Hypervitaminosis A (complications, physiopathology)
• NF-E2-Related Factor 2 (metabolism)
• Protein Transport
• Signal Transduction
• Transcription Factors (metabolism)
• Transcriptome (drug effects)
• Vitamin A (pharmacology)