Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal Metaplasia.

Background & aims Metaplasia in the stomach is highly associated with development of intestinal-type gastric cancer. Two types of metaplasias, spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia (IM) are considered precancerous lesions. However, it remains unclear how SPEM and IM are related. Here, we investigated a new lineage-specific marker for SPEM cells, aquaporin 5 (AQP5), to assist in the identification of these two metaplasias. Methods Drug- or Helicobacter felis (H. felis) infection-induced mouse models were used to identify the expression pattern of AQP5 in acute or chronic SPEM. Gene-manipulated mice treated with or without drug were employed to investigate how AQP5 expression is regulated in metaplastic lesions. Metaplastic samples from transgenic mice and human gastric cancer patients were evaluated for AQP5 expression. Immunostaining with lineage-specific markers was used to differentiate metaplastic gland characteristics. Results Our results revealed that AQP5 is a novel lineage-specific marker for SPEM cells which are localized at the base of metaplastic glands initially and expand to dominate glands after chronic H. felis infection. Additionally, AQP5 expression was upregulated early in chief cell reprogramming and was promoted by interleukin-13 (IL-13). In humans, metaplastic corpus showed highly branched structures with AQP5-positive SPEM. Human SPEM cells strongly expressing AQP5 were present at the bases of incomplete IM glands marked by TROP2, but were absent from complete IM glands. Conclusions AQP5-expressing SPEM cells are present in pyloric metaplasia and TROP2-positive incomplete IM and may be an important component of metaplasia which can predict a higher risk for gastric cancer development.