Differential gene expression in Glisson's capsule associated with liver abscesses in feedlot cattle

Liver abscesses (LA) in feedlot cattle are associated with reduced growth performance, increased liver and offal condemnations, and carcass value losses; however, potential animal welfare impacts, including pain, remain poorly understood. Although liver parenchyma lacks pain receptors, stretching or inflammation of the surrounding Glisson's capsule is known to cause pain in humans. As the liver swells in response to LA, expansion of Glisson's capsule may activate nociceptive pathways. Our objective was to compare gene expression in Glisson's capsule from livers with (n = 6) and without LA (n = 9) to identify molecular signatures associated with LA. RNA was extracted from Glisson's capsule tissue, sequenced on an Illumina platform, aligned to the Bos taurus reference genome using HISAT2, and quantified with featureCounts. Differential gene expression was assessed using DESeq2 (FDR ≤ 0.05; |log2 FC| ≥ 1). Sixty genes were differentially expressed; 41 were upregulated and 19 were downregulated in ABS tissue. FOS (+1.6 log2FC) and FOSB (+2.4 log2FC), molecular markers associated with acute and chronic pain, respectively, were upregulated in animals with LA. ENSBTAG00000061094, the bovine ortholog of human MRP4, had the greatest differential expression (-4.5 log2FC) and was downregulated in animals with LA; MRP4 is involved in inflammatory mediator transport and altered inflammatory pain thresholds. SNCA (-2.1 log2FC) has been associated with pain hypersensitivity and was downregulated in animals with LA, whereas ISG12(B) (+3.3 log2FC) indicated heightened innate immune and mitochondrial apoptotic activity and was upregulated in animals with LA. Increased EPHB3 (+1.8 log2FC) was upregulated in animals with LA and is consistent with signaling implicated in inflammatory remodeling and peripheral neuroimmune pain pathways. This study provides the first characterization of gene expression changes in Glisson's capsule associated with bovine LA. Differentially expressed genes related to inflammation, nociceptive signaling, and tissue stress suggest that LA create an inflamed and likely pain-relevant molecular environment within the liver capsule. Further research is needed to confirm whether these molecular changes correspond to perceived pain in cattle.