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Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4

Glucosaminyl N-deacetylase/N-sulfotransferases (NDSTs) are the first enzymes that mediate the initiation of heparan sulfate sulfation. We previously identified NDST4 as a putative tumor suppressor in human colorectal cancer. In the study, we generated an Ndst4 knockout (Ndst4(−/−)) mouse strain and...

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Autores principales: Jao, Tzu-Ming, Li, Ya-Lin, Lin, Shu-Wha, Tzeng, Sheng-Tai, Yu, I-Shing, Yen, Sou-Jhy, Tsai, Ming-Hong, Yang, Ya-Chien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356710/
https://www.ncbi.nlm.nih.gov/pubmed/27793051
http://dx.doi.org/10.18632/oncotarget.12915
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author Jao, Tzu-Ming
Li, Ya-Lin
Lin, Shu-Wha
Tzeng, Sheng-Tai
Yu, I-Shing
Yen, Sou-Jhy
Tsai, Ming-Hong
Yang, Ya-Chien
author_facet Jao, Tzu-Ming
Li, Ya-Lin
Lin, Shu-Wha
Tzeng, Sheng-Tai
Yu, I-Shing
Yen, Sou-Jhy
Tsai, Ming-Hong
Yang, Ya-Chien
author_sort Jao, Tzu-Ming
collection PubMed
description Glucosaminyl N-deacetylase/N-sulfotransferases (NDSTs) are the first enzymes that mediate the initiation of heparan sulfate sulfation. We previously identified NDST4 as a putative tumor suppressor in human colorectal cancer. In the study, we generated an Ndst4 knockout (Ndst4(−/−)) mouse strain and explored its phenotypic characteristics, particularly in the development of colonic epithelial homeostasis. The Ndst4-deficient mice were viable and fertile, and their life spans were similar to those of wild-type littermates. No gross behavioral or morphological differences were observed between the Ndst4(−/−) and wild-type mice, and no significant changes were determined in the hematological or serum biochemical parameters of the Ndst4(−/−) mice. Ndst4 RNA transcripts were expressed in the brain, lung, gastrointestinal tract, pancreas, and ovary. However, Ndst4-null mice exhibited no gross or histological abnormalities in the studied organs, except for the colon. Although no alterations were observed in the crypt length or number of proliferating cells, the Ndst4(−/−) mice exhibited an increased number of goblet cells and a decreased number of colonocytes in the proximal colon compared with the wild-type mice. Moreover, Ndst4 deficiency increased the basal level of apoptosis in the colonic epithelium. Taken together, we established, for the first time, an Ndst4(−/−) mouse strain and revealed the involvement of Ndst4 in the development and homeostasis of colonic epithelium. Accordingly, NDST4 in human colon might direct the biosynthesis of specific heparan sulfate proteoglycans that are essential for the maintenance of colonic epithelial homeostasis. Thus, the loss of its function may result in the tumorigenesis and progression of colorectal cancer.
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spelling pubmed-53567102017-04-26 Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4 Jao, Tzu-Ming Li, Ya-Lin Lin, Shu-Wha Tzeng, Sheng-Tai Yu, I-Shing Yen, Sou-Jhy Tsai, Ming-Hong Yang, Ya-Chien Oncotarget Research Paper Glucosaminyl N-deacetylase/N-sulfotransferases (NDSTs) are the first enzymes that mediate the initiation of heparan sulfate sulfation. We previously identified NDST4 as a putative tumor suppressor in human colorectal cancer. In the study, we generated an Ndst4 knockout (Ndst4(−/−)) mouse strain and explored its phenotypic characteristics, particularly in the development of colonic epithelial homeostasis. The Ndst4-deficient mice were viable and fertile, and their life spans were similar to those of wild-type littermates. No gross behavioral or morphological differences were observed between the Ndst4(−/−) and wild-type mice, and no significant changes were determined in the hematological or serum biochemical parameters of the Ndst4(−/−) mice. Ndst4 RNA transcripts were expressed in the brain, lung, gastrointestinal tract, pancreas, and ovary. However, Ndst4-null mice exhibited no gross or histological abnormalities in the studied organs, except for the colon. Although no alterations were observed in the crypt length or number of proliferating cells, the Ndst4(−/−) mice exhibited an increased number of goblet cells and a decreased number of colonocytes in the proximal colon compared with the wild-type mice. Moreover, Ndst4 deficiency increased the basal level of apoptosis in the colonic epithelium. Taken together, we established, for the first time, an Ndst4(−/−) mouse strain and revealed the involvement of Ndst4 in the development and homeostasis of colonic epithelium. Accordingly, NDST4 in human colon might direct the biosynthesis of specific heparan sulfate proteoglycans that are essential for the maintenance of colonic epithelial homeostasis. Thus, the loss of its function may result in the tumorigenesis and progression of colorectal cancer. Impact Journals LLC 2016-10-26 /pmc/articles/PMC5356710/ /pubmed/27793051 http://dx.doi.org/10.18632/oncotarget.12915 Text en Copyright: © 2016 Jao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Jao, Tzu-Ming
Li, Ya-Lin
Lin, Shu-Wha
Tzeng, Sheng-Tai
Yu, I-Shing
Yen, Sou-Jhy
Tsai, Ming-Hong
Yang, Ya-Chien
Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4
title Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4
title_full Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4
title_fullStr Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4
title_full_unstemmed Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4
title_short Alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl N-deacetylase/N-sulfotransferase 4
title_sort alteration of colonic epithelial cell differentiation in mice deficient for glucosaminyl n-deacetylase/n-sulfotransferase 4
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356710/
https://www.ncbi.nlm.nih.gov/pubmed/27793051
http://dx.doi.org/10.18632/oncotarget.12915
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