Transcriptome Analysis Reveals Anti-inflammatory, Antiapoptotic, and Milk Synthesis-Promoting Effects of Lithium...

Lithium, an essential trace element in higher animals, has anti-inflammatory, anti-apoptotic, and nutritional roles. The mechanism by which lithium chloride (LiCl) promotes milk synthesis has been partially elucidated in our previous study; however, potential regulators remain to be identified, and the potential properties of LiCl to inhibit inflammation and apoptosis in bovine mammary epithelial (MAC-T) cells are yet to be clarified. This study aimed to investigate the effects of LiCl on MAC-T cells induced by differentiation using RNA sequencing technology. A total of 237 differentially expressed genes (DEGs) were identified. Through functional annotation using gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis, we identified several genes associated with LiCl function. These genes include inflammation-related genes such as FOSB, C1QTNF1, ANKRD1, DUSP10, ATF3, FAP, and FGF18; apoptosis-related genes such as FAP, FGF18, TMEM170B, and TBX20; milk fat synthesis-related gene FABP9; and milk protein synthesis-related genes TMEM170B, TBX20, FCER1G, and C1QTNF1. Additionally, we found KRT35, a gene that may promote cell proliferation. The aforementioned genes were confirmed via qPCR, and the expression levels of inflammation-related genes pointing to NF-κB (p65) and cellular pro-inflammatory factors TNFα, IL- 1β, IL- 6, and IL- 8 were determined. Following a comprehensive analysis, we hypothesized that in MACT cells, LiCl could inhibit the transcription of inflammatory cytokines genes through inhibition of NF-κB and MAPK signaling pathways to exert anti-inflammatory effects, and increase milk protein and milk fat synthesis through Wnt/β-catenin and mTOR signaling pathways through the differences in gene expression.