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GASTROENTEROLOGY: PLE(ase) pass on the heparin: A new compound stems the tide of protein loss from the gut

Protein-losing enteropathy (PLE) is a dangerous condition involving protein leakage from the gut. Administration of heparin, which stops blood from clotting, can be used to treat individuals with the disorder, since heparin-related molecules (such as HS and Sdc1) are shed by the gut lining cells during episodes of PLE. However, the precise mechanisms of action of heparin as a treatment for PLE are unknown, and its serious side effects make long-term use unrealistic. In a new study, Hudson Freeze and his colleagues at the Burnham Institute for Medical Research, La Jolla, have identified a new, safe, and effective therapy for PLE-like disease in mice.

The authors generated mice lacking Sdc and mice lacking HS in the intestines, and found that these mice leaked protein from their gut, indicating that these molecules are essential for maintaining the integrity of the intestine and making the mice a good model to study intestinal protein leakage. Protein loss from the intestines of these mice was further increased by injection of the proteins IFN-gamma or TNF-alpha, and/or by increased venous blood pressure, all of which are known to be key players in PLE development. Treating the mice with either heparin or a modified heparin molecule that does not stop blood clotting effectively reduced protein leakage from the gut, leading the authors to recommend clinical testing of this molecule in the treatment of PLE.

TITLE: Heparan sulfate and syndecan-1 are essential in maintaining murine and human intestinal epithelial barrier function

AUTHOR CONTACT: Hudson H. Freeze
Burnham Institute for Medical Rese
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