The gallbladder-specific proteome
The gallbladder is a hollow sac-shaped organ situated below the liver. The main function of the gallbladder is to store and release bile, a yellow-brown liquid, produced by liver hepatocytes, that is important for the digestion of fats. The bile-filled interior space of the gallbladder is directly connected to the duodenum to where the bile is released during digestion. During the storage, water and electrolytes are removed from the bile through an active sodium ion transport across the simple columnar epithelium of the gallbladder, in order to concentrate the bile. Transcriptome analysis shows that 68% (n=13670) of all human proteins (n=20162) are expressed in the gallbladder and 88 of these genes show an elevated expression in the gallbladder compared to other tissue types.
The gallbladder transcriptome
Transcriptome analysis of the gallbladder can be visualized with regard to the specificity and distribution of transcribed mRNA molecules (Figure 1). Specificity illustrates the number of genes with elevated or non-elevated expression in the gallbladder compared to other tissues. Elevated expression includes three subcategory types of elevated expression:
Distribution, on the other hand, visualizes how many genes have, or do not have, detectable levels (nTPM≥1) of transcribed mRNA molecules in the gallbladder compared to other tissues. As evident in Table 1, all genes elevated in gallbladder are categorized as:
Figure 1. (A) The distribution of all genes across the five categories based on transcript specificity in gallbladder as well as in all other tissues. (B) The distribution of all genes across the six categories, based on transcript detection (nTPM≥1) in gallbladder as well as in all other tissues.
Table 1. The number of genes in the subdivided categories of elevated expression in gallbladder.
Protein expression of genes elevated in gallbladder
In-depth analysis of the elevated genes in the gallbladder using antibody-based protein profiling allowed us to visualize the expression patterns of these proteins within the gallbladder. The gallbladder is part of the biliary system which refers to the liver, gallbladder and bile ducts. Examples of proteins with elevated expression in the gallbladder include CHST4 and LGALS2.
CHST4, also known as carbohydrate sulfotransferase 4, is an enzyme that is involved in the sulfation of carbohydrates. Sulfate groups added to carbohydrates (GAGs) by CHST4 can affect the overall charge and structure of GAGs, which will affect their interactions with e.g. growth factors, cell surface receptors important in cell signaling, tissue development and inflammation.
Galectin-2 (LGALS2) is a protein expressed in multiple tissues and organs, e.g. gastrointestinal tract and the immune system. The galectin family have the ability to bind to specific carbohydrate structures (β-galactoside residues) to reglate processes including cell adhesion, immune regulation and inflammation.
Gene expression shared between gallbladder and other tissues
There are 16 group enriched genes expressed in gallbladder. Group enriched genes are defined as genes showing a 4-fold higher average level of mRNA expression in a group of 2-5 tissues, including gallbladder, compared to all other tissues.
To illustrate the relation of gallbladder tissue to other tissue types, a network plot was generated, displaying the number of genes with a shared expression between different tissue types.
Figure 2. An interactive network plot of the gallbladder enriched and group enriched genes connected to their respective enriched tissues (grey circles). Red nodes represent the number of gallbladder enriched genes and orange nodes represent the number of genes that are group enriched. The sizes of the red and orange nodes are related to the number of genes displayed within the node. Each node is clickable and results in a list of all enriched genes connected to the highlighted edges. The network is limited to group enriched genes in combinations of up to 5 tissues, but the resulting lists show the complete set of group enriched genes in the particular tissue.
Gallbladder has most group enriched gene expression in common with intestine, stomach and liver. Examples of proteins with shared expression in the gallbladder and other tissues include TM4SF4 and ACE2.
The main function of the gallbladder is to concentrate, store and release bile into the small intestine. Bile is a yellow-brown liquid produced by the hepatocytes in the liver. The release of bile is stimulated by the presence of dietary fats in the small intestine where it acts as a surfactant to emulsify and digest lipids from the food.
The gallbladder sac is attached to the posterior surface of the right lobe of the liver. It is divided into the fundus, body and neck.
The wall of the gallbladder is composed of three layers: mucosa, muscularis, and serosa. There are no muscularis mucosae or submucosa. The mucosa is made up of branching folds lined by a single layer of columnar cells having a pale cytoplasm. The lamina propria encompasses loose connective tissue, blood vessels, nerves, and sparse plasma cells. The muscularis is made up of randomly distributed smooth muscle fibers.
Here, the protein-coding genes expressed in gallbladder are described and characterized, together with examples of immunohistochemically stained tissue sections that visualize corresponding protein expression patterns of genes with elevated expression in gallbladder.
Transcript profiling was based on a combination of two transcriptomics datasets (HPA and GTEx), corresponding to a total of 14590 samples from 50 different human normal tissue types. The final consensus normalized expression (nTPM) value for each tissue type was used for the classification of all genes according to the tissue-specific expression into two different categories, based on specificity or distribution.
Relevant links and publications
Uhlén M et al., Tissue-based map of the human proteome. Science (2015)