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

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 unclea...

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Autores principales:	Su-Hyung Lee, Bogun Jang, Jimin Min, Ela W. Contreras-Panta, Kimberly S. Presentation, Alberto G. Delgado, M. Blanca Piazuelo, Eunyoung Choi, James R. Goldenring
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	AQP5 Gastric Cancer IM TROP2 SPEM Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/a0b008990421406eb518941db7b2bc23
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spelling	oai:doaj.org-article:a0b008990421406eb518941db7b2bc232021-11-14T04:34:16ZUp-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary2352-345X10.1016/j.jcmgh.2021.08.017https://doaj.org/article/a0b008990421406eb518941db7b2bc232022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001843https://doaj.org/toc/2352-345XBackground & 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 2 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 used 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 that are localized at the base of metaplastic glands initially and expand to dominate glands after chronic H felis infection. In addition, AQP5 expression was up-regulated early in chief cell reprogramming and was promoted by interleukin 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 that can predict a higher risk for gastric cancer development.Su-Hyung LeeBogun JangJimin MinEla W. Contreras-PantaKimberly S. PresentationAlberto G. DelgadoM. Blanca PiazueloEunyoung ChoiJames R. GoldenringElsevierarticleAQP5Gastric CancerIMTROP2SPEMDiseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 13, Iss 1, Pp 199-217 (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	AQP5 Gastric Cancer IM TROP2 SPEM Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	AQP5 Gastric Cancer IM TROP2 SPEM Diseases of the digestive system. Gastroenterology RC799-869 Su-Hyung Lee Bogun Jang Jimin Min Ela W. Contreras-Panta Kimberly S. Presentation Alberto G. Delgado M. Blanca Piazuelo Eunyoung Choi James R. Goldenring Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary
description	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 2 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 used 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 that are localized at the base of metaplastic glands initially and expand to dominate glands after chronic H felis infection. In addition, AQP5 expression was up-regulated early in chief cell reprogramming and was promoted by interleukin 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 that can predict a higher risk for gastric cancer development.
format	article
author	Su-Hyung Lee Bogun Jang Jimin Min Ela W. Contreras-Panta Kimberly S. Presentation Alberto G. Delgado M. Blanca Piazuelo Eunyoung Choi James R. Goldenring
author_facet	Su-Hyung Lee Bogun Jang Jimin Min Ela W. Contreras-Panta Kimberly S. Presentation Alberto G. Delgado M. Blanca Piazuelo Eunyoung Choi James R. Goldenring
author_sort	Su-Hyung Lee
title	Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary
title_short	Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary
title_full	Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary
title_fullStr	Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary
title_full_unstemmed	Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary
title_sort	up-regulation of aquaporin 5 defines spasmolytic polypeptide-expressing metaplasia and progression to incomplete intestinal metaplasiasummary
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/a0b008990421406eb518941db7b2bc23
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Up-regulation of Aquaporin 5 Defines Spasmolytic Polypeptide-Expressing Metaplasia and Progression to Incomplete Intestinal MetaplasiaSummary

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