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BMC Gastroenterol. 2015 Jul 8;15:77. doi: 10.1186/s12876-015-0311-5.

IGF-1 decreases portal vein endotoxin via regulating intestinal tight junctions and plays a role in attenuating portal hypertension of cirrhotic rats.

Author information

1
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. wwwdxycnbbs@163.com.
2
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. 1304133485@qq.com.
3
Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, 116023, Dalian, Liaoning province, China. machuye2008@163.com.
4
Department of Clinical Pharmacology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. hanhanjiayoudl@163.com.
5
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. cathydoctor@sina.com.
6
Department of Infectious Diseases, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. zhuyingsh52@126.com.
7
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. zhaogang_59@263.net.
8
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. Chunyanlidl@163.com.
9
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. wenwensl@yeah.net.
10
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, 116000, Dalian, Liaoning province, China. yd613@163.com.

Abstract

BACKGROUND:

Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines.

METHODS:

We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings.

RESULTS:

Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells.

CONCLUSIONS:

Tight junction dysfunction develops during the development of liver cirrhosis, and endotoxemia will develop subsequently. Correspondingly, increased endotoxin in portal system worsens tight junction dysfunction via decreasing intestinal occludin and claudin-1 expressions and increasing enterocytic apoptosis. Endotoxemia and intestinal barrier dysfunction form a vicious circle. External administration of IGF-1 breaks this vicious circle. Improvement of tight junctions might be one possible mechanism of the restoration of intestinal barrier function mediated by IGF-1.

PMID:
26152281
PMCID:
PMC4495682
DOI:
10.1186/s12876-015-0311-5
[Indexed for MEDLINE]
Free PMC Article

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