Podoplanin hetero-insufficiency mice with inflammation in the jejunum demonstrates a good animal model of congenital protein-losing enteropathy

TL;DR

This study shows that Podoplanin-deficient mice with intestinal inflammation mimic a rare digestive disease called congenital protein-losing enteropathy.

Contribution

The study introduces a novel mouse model combining Podoplanin heterozygosity and jejunal inflammation to study congenital PLE.

Findings

Podoplanin hetero-insufficiency mice with jejunal inflammation show hypoalbuminemia and albumin leakage into the gut.

Lymphangiectasia in jejunal villi disrupts lymph flow and albumin retention in the mice model.

The model exhibits symptoms similar to those observed in human congenital PLE patients.

Abstract

We have identified the Podoplanin expression in rat jejunal villi. We aimed to investigate the relationship between the Podoplanin expression in jejunal villi and the pathogenesis of congenital protein-losing enteropathy (PLE), using the Podoplanin heterozygous knock-out (Pdpn-het KO) mice and aspirin-induced inflammation of the jejunum. In the Pdpn-het KO mice the reticular and complexes distribution of Podoplanin was observed in the jejunal villi, resulting in be swollen of lamina propria. To confirm the abnormal distribution of small lymph vessels in the jejunal villi, the LYVE-1 immunohistochemical expression was investigated. The expression of Podoplanin and LYVE-1 in the jejunum of the Pdpn-het KO mice exhibited a distinct pattern. The intravenous administration of Evans blue dye appeared quickly into the mesenteric lymph vessels and lymph nodes in the wild-type but not observed in Pdpn-het KO mice. In the Pdpn-het KO mice, aspirin-induced jejunal inflammation produced a significant leakage of the intravenous administration of FITC-albumin into the jejunal lumen. The hypoalbuminemia in the blood and the marked distribution of FITC-albumin in the jejunal villi were also observed in the mice. In conclusion, we proposed that Pdpn-het KO mice with jejunal inflammation demonstrates a good animal model of the congenital PLE.

Graphical abstract of the conclusion in the present study. In the Pdpn-het KO mice, the aspirin-induced jejunal inflammation resulted in a significant leakage of the FITC-albumin into the jejunal lumen, resulted in the induction of marked hypoalbuminemia. In addition, the lymphangiectasia was confirmed in the lamina propria of jejunal villi, which disturbed mesenteric lymph flow and stored permeant albumin in jejunal villi. Thus, the Pdpn-het KO mice may be a good animal model of congenital PLE.ga1

Graphical abstract of the conclusion in the present study. In the Pdpn-het KO mice, the aspirin-induced jejunal inflammation resulted in a significant leakage of the FITC-albumin into the jejunal lumen, resulted in the induction of marked hypoalbuminemia. In addition, the lymphangiectasia was confirmed in the lamina propria of jejunal villi, which disturbed mesenteric lymph flow and stored permeant albumin in jejunal villi. Thus, the Pdpn-het KO mice may be a good animal model of congenital PLE.

•Podoplanin hetero-insufficiency mice with jejunal inflammation demonstrates the similar symptom in the patients of congenital PLE.•Based on the findings, podoplanin hetero-insufficiency mice with jejunal inflammation demonstrates a good animal model of the PLE.

Podoplanin hetero-insufficiency mice with jejunal inflammation demonstrates the similar symptom in the patients of congenital PLE.

Based on the findings, podoplanin hetero-insufficiency mice with jejunal inflammation demonstrates a good animal model of the PLE.

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