Background: Gallbladder mucocele (GBM) is one of the most common diseases that occur in canine gallbladder. Although the pathogenesis of GBM remains unclear, we have recently reported that the excessive accumulation of mucin in the gallbladder is not due to its overproduction by gallbladder epithelial cells (GBECs). Hypothesis/
Objectives: We hypothesized that the changes in the functions of GBECs other than the production of mucin were associated with the pathogenesis of GBM. The objective was set to investigate the abnormalities in gene expression profiles of GBECs in cases with GBM. Animals: Fifteen dogs with GBM and eight dogs euthanized for reasons other than gallbladder diseases were included.
Methods: GBECs were isolated from gallbladder tissues, and RNA was extracted from GBECs. RNA-seq was performed using the samples of three GBM cases and three dogs with normal gallbladder, and the gene expression profiles were compared between the two groups. The differences in mRNA expression levels of the extracted differentially expressed genes (DEGs) were validated between the two groups using the samples of fifteen GBM cases and eight dogs with normal gallbladder.
Results: Comparison of gene expression profiles by RNA-seq extracted 367 DEGs, including ANO1, a chloride channel associated with changes in mucin morphology, and HTR4, which regulates the function of chloride channels. ANO1 and HTR4 were confirmed to be downregulated in the GBM group by RT-qPCR.Conclusions and clinical importance: The results of this study suggest that GBM can be developed by the decreased function of chloride channels expressed in GBECs.
.jpg "Itsuma Nagao, DVM (he/him/his) photo")