322. Differential Gene Expression in Glisson’s Capsule Associated with Liver Abscesses in Feedlot Cattle.

Abstract Liver abscesses (LA) in feedlot cattle, often observed at harvest, are associated with reduced growth performance, increased liver and offal condemnation rates, and carcass value losses. Although etiologies of LA are well described, potential animal welfare impacts, including pain, remain poorly understood. The liver parenchyma does not have pain receptors, however numerous human medical reports indicate that stretching or inflammation of the Glisson’s capsule can cause significant pain. As livers swell in response to LA, the resulting expansion stretches the Glisson’s capsule, likely activating nociceptive pathways. Our objective was to evaluate gene expression of Glisson’s capsules from livers with and without LA to determine if LA induce different molecular signatures. Capsule tissue was excised from the surface of LA (n = 6), and from livers without LA (n = 9), then immediately frozen on dry ice. RNA was extracted using a TRIzol-based approach, sequenced on an Illumina platform, aligned to the Bos taurus reference using HISAT2, and quantified with featureCounts. Differential gene expression was assessed using DESeq2, with significance defined as FDR ≤ 0.05. Sixty genes were differentially expressed between LA groups; 41 genes were upregulated and 19 were downregulated in the LA-affected group. Of the 60 genes evaluated, 19 are associated with liver disease, 15 are associated with liver cancer, 8 are associated with inflammation, 8 are associated with liver tissue regeneration and extracellular remodeling, and 4 are associated with pain signaling pathways (FOS, FOSB, MRP4, and SNCA). Notably, FOS {upregulated 1.6 log2 fold change (FC)} and FOSB (upregulated 2.4 log2FC), are well-established molecular markers of acute and chronic pain, respectively. The gene with the largest overall differential expression (-4.5 log2FC) was ENSBTAG00000061094, the bovine ortholog of human MRP4, which has known roles in inflammatory mediator transport and has been linked to altered inflammatory pain thresholds. Down regulation of this gene has been associated with inhibition of inflammation, tissue regeneration, and increased pain thresholds. Expression of SNCA (-2.1 log2FC) has been associated with pain hypersensitivity in the presence of tumors. Other notable differentially expressed genes include ISG12(B) (highest upregulated gene, +3.3 log2FC), which indicates heightened innate immune and mitochondrial apoptotic activity, whereas increased EPHB3 expression (+1.8 log2FC) is consistent with enhanced ephrin-B signaling which has been 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. Several genes are associated with inflammation, nociceptive signaling, and tissue stress. These results suggest that LA cause a more inflamed and potentially pain-relevant molecular environment within the liver capsule. Whether or not these molecular changes correspond to perceived pain in cattle will require further investigation.