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Published on: September 15, 2017
Gene Networks and Pathways Involved in LPS-Induced Proliferative Response of Bovine Endometrial Epithelial Cells
Mojtaba Najafi1,2, Yongzhi Guo3, Göran Andersson2
1Department of Animal Sciences, Gorgan Agricultural Sciences and Natural Resources University, Golestan 4913815739, Iran.
Insights
Lipopolysaccharide (LPS) from bacteria triggers bovine endometrial cell proliferation and inflammation. Bioinformatic analysis identified key transcription factors and pathways, revealing insights into LPS-induced endometrial cancer and immune responses.
Area of Science:
- Veterinary immunology
- Molecular biology
- Bioinformatics
Background:
- Lipopolysaccharide (LPS) from Gram-negative bacteria causes mastitis and metritis in dairy cattle.
- LPS induces bovine endometrial epithelial cell proliferation and inflammation.
- Previous transcriptomic studies identified differentially expressed genes (DEGs) in response to LPS.
Purpose of the Study:
- To decipher gene networks involved in LPS-induced proliferation and apoptosis in bovine endometrial epithelial cells.
- To understand the mechanisms underlying LPS effects on endometrial cells.
- To gain insights into early signaling and metabolic pathways in response to Escherichia coli LPS infection.
Main Methods:
- Bioinformatic analysis of RNA-sequencing data from primary bovine endometrial epithelial cells exposed to LPS.
- Identification of differentially expressed genes (DEGs) and putative transcription factors (TFs).
- Analysis of gene network interactions and associated signaling pathways.
Main Results:
- 116 putative transcription factors were identified, with significant interactions involving NFKβ1, TP53, STAT1, and HIF1A.
- LPS challenge induced a strong transcriptomic response with potent activation of pro-inflammatory pathways.
- Identified pathways include Toll-like receptor, NFKβ, AKT, apoptosis, and MAPK signaling, linked to endometrial cancer.
Conclusions:
- LPS significantly impacts bovine endometrial epithelial cells, driving proliferation and inflammation.
- Key transcription factors and signaling pathways mediate the cellular response to LPS infection.
- Findings provide mechanistic explanations for LPS-associated endometrial cancer and immune responses in cattle.
Abstract:
Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria involved in the pathogenic processes leading to mastitis and metritis in animals such as dairy cattle. LPS causes cell proliferation associated with endometrium inflammation. Former in vitro studies have demonstrated that LPS induces an intense stimulation of the proliferation of a pure population of bovine endometrial epithelial cells. In a follow-up transcriptomic study based on RNA-sequencing data obtained after 24 h exposure of primary bovine endometrial epithelial cells to 0, 2, and 8 μg/mL LPS, 752 and 727 differentially expressed genes (DEGs) were detected between the controls and LPS-treated samples that encode proteins known to be associated with either proliferation or apoptosis, respectively. The present bioinformatic analysis was performed to decipher the gene networks involved to obtain a deeper understanding of the mechanisms underlying the proliferative and apoptosis processes. Our findings have revealed 116 putative transcription factors (TFs) and the most significant number of interactions between these TFs and DEGs belong to NFKβ1, TP53, STAT1, and HIF1A. Moreover, our results provide novel insights into the early signaling and metabolic pathways in bovine endometrial epithelial cells associated with the innate immune response and cell proliferation to Escherichia coli-LPS infection. The results further indicated that LPS challenge elicited a strong transcriptomic response, leading to potent activation of pro-inflammatory pathways that are associated with a marked endometrial cancer, Toll-like receptor, NFKβ, AKT, apoptosis, and MAPK signaling pathways. This effect may provide a mechanistic explanation for the relationship between LPS and cell proliferation.
