Salivary epithelial cells: an unassuming target site for gene therapeutics

Abstract

Salivary glands are classical exocrine glands whose external secretions result in the production of saliva. However, in addition to the secretion of exocrine proteins, salivary epithelial cells are also capable of secreting proteins internally, into the bloodstream. This brief review examines the potential for using salivary epithelial cells as a target site for in situ gene transfer, with an ultimate goal of producing therapeutic proteins for treating both systemic and upper gastrointestinal tract disorders. The review discusses the protein secretory pathways reported to be present in salivary epithelial cells, the viral gene transfer vectors shown useful for transducing these cells, model transgenic secretory proteins examined, and some clinical conditions that might benefit from such salivary gland gene transfer.

Figure 1

General depiction of protein secretory pathways operative in salivary epithelial cells. The regulated pathway leads to exocrine protein secretion via secretory granules (circles at the apical pole of the cell). Endocrine secretion presumably occurs via a constitutive or constitutive-like pathway. TJ, tight junctions.

Figure 2

Locations of marker proteins in or relevant to the protein secretory pathway in salivary epithelial cells. Secretory granules (SG); inmature secretory granules (ISG); trans-golgi network (TGN). Markers that can be used to characterize the location of a secretory protein in specific salivary gland organelles are indicated. These include aquaporin −5 (AQP-5); early Endosome antigen 1 (EEA-1); RAB GTPases 4/5/11 (RAB-4/5/11); endoplasmic reticulum-associated protein disulfide isomerase (PDI); Na-K-Cl co-transporter 1 (NKCC1); 36-kD vesicular integral membrane protein (VIP-36); glutamic acid/glutamine-rich protein (GRP); vesicle-associated membrane protein 4/8 (VAMP-4/8); type I integral membrane protein from the trans-Golgi network (TGN-38); lysosomal-associated membrane protein (LAMP1); Golgi matrix protein (GM-130).