Oncotarget

Research Papers:

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

Tzu-Ming Jao, Ya-Lin Li, Shu-Wha Lin, Sheng-Tai Tzeng, I-Shing Yu, Sou-Jhy Yen, Ming-Hong Tsai _ and Ya-Chien Yang

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Oncotarget. 2016; 7:84938-84950. https://doi.org/10.18632/oncotarget.12915

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Abstract

Tzu-Ming Jao1, Ya-Lin Li1, Shu-Wha Lin1,2, Sheng-Tai Tzeng1, I-Shing Yu3, Sou-Jhy Yen4, Ming-Hong Tsai4,5, Ya-Chien Yang1,2

1Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan

2Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan

3Laboratory Animal Center, National Taiwan University College of Medicine, Taipei, Taiwan

4Department of Surgery, Cardinal Tien Hospital, New Taipei City, Taiwan

5School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

Correspondence to:

Ming-Hong Tsai, email: tsai110008@yahoo.com.tw

Ya-Chien Yang, email: ycyangntu@ntu.edu.tw

Keywords: NDST4, tumor suppressor gene, heparan sulfate proteoglycan, Ndst4 knockout mouse

Received: July 29, 2016     Accepted: October 14, 2016     Published: October 26, 2016

ABSTRACT

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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