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The Jagged-1/Notch-1/Hes-1 pathway is involved in intestinal adaptation in a massive small bowel resection rat model.

Abstract：

BACKGROUND:Notch signaling is required for the maintenance of intestinal epithelial proliferation. Dysfunction of this signaling pathway is associated with the loss of proliferated crypt epithelial cells. AIM:The aim of this study was to investigate the role of Notch signaling in small bowel resection (SBR)-associated crypt epithelial cell proliferation. METHODS:Male Sprague-Dawley rats were subjected to sham operation (bowel transection and reanastomosis) or 70% mid-SBR. Intestinal tissue samples were collected at 0.5, 1, 6, 12, 24, 72, and 168 h after operation. The expression of Notch pathway mRNAs and proteins was analyzed using RT-PCR and Western blot. The expression of the Notch pathway proteins Jagged-1, NICD and Hes-1 was also determined through immunohistochemical staining using day 3 postoperative intestinal tissues. The degree of crypt epithelial cell proliferation was evaluated using the immunohistochemical staining of proliferating cell nuclear antigen (PCNA). Furthermore, IEC-6 cells were used to examine the function of the Jagged-1 signaling system. RESULTS:SBR led to increased crypt epithelial cell proliferation and increased expression of Jagged-1 and Hes-1 mRNA and protein along with cleaved Notch-1. Immunohistochemical staining showed that Jagged-1, cleaved Notch-1 and Hes-1 colocalized in the same proliferated crypt epithelial cell population. Recombinant Jagged-1 significantly stimulated the proliferation of IEC-6 cells. Transient upregulation of Jagged-2 expression was found 1 h after SBR, and it was accompanied by cleaved Notch-1 and Hes-1 upregulation. CONCLUSION:The Jagged-1/Notch-1/Hes-1 signaling pathway is involved in intestinal adaptation through increasing crypt epithelial cell proliferation.

journal_name

Dig Dis Sci

journal_title

Digestive diseases and sciences

authors

Chen G,Sun L,Yu M,Meng D,Wang W,Yang Y,Yang H

doi

10.1007/s10620-013-2680-3

subject

Has Abstract

pub_date

2013-09-01 00:00:00

pages

2478-86

issue

9

eissn

0163-2116

issn

1573-2568

journal_volume

58

pub_type

杂志文章

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