High glucose‐induced intestinal epithelial barrier damage is aggravated by syndecan‐1 destruction and heparanase overexpression

Journal of Cellular and Molecular Medicine

Qing Qing³  Shaoheng Zhang¹  Ye Chen²  Runhua Li²  Hua Mao¹ 

[1] Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, China;Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou, China;Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

关键词: high glucose;    diabetes;    syndecan‐1;    heparanase;    intestinal epithelial barrier;   

DOI  :  10.1111/jcmm.12523

来源: Wiley

【 摘 要 】

Abstract

Syndecan-1 (Sdc1) and its endo-beta-d-glucuronidase heparanase (HPSE) are implicated in maintenance of intestinal epithelial barrier (IEB), but their alterations and roles in high-glucose/hyperglycaemia (HG) conditions have not been fully investigated. This study aimed to determine the expression pattern, the possible regulation mechanism of Sdc1 and HPSE in HG conditions, and their potential effects on IEB. Therefore, diabetic mice/cell models were developed, and tissue/serum samples, cell lysate and culture supernatants were harvested. The expression of Sdc1 and HPSE in control, HG and designated interventions groups were detected. Phosphorylations of mitogen-activated protein kinase signalling pathway (MAPK), the expressions of Occludin and ZO-1, and the levels of transepithelial electrical resistance (TEER) were measured and monitored. The results showed that in HG conditions, intestinal tissue and cellular Sdc1 were significantly decreased, but the expression of HPSE, and soluble Sdc1 in serum and culture supernatants were remarkably increased. Such alterations of Sdc1 and HPSE were associated with solely p38 MAPK activation, and were correlated with the reductions of Occludin, ZO-1 and TEER. Heparin (Sdc1 analogue) and SB203580 (a p38 MAPK inhibitor), instead of insulin, alleviated Sdc1 destruction and HPSE overexpression, and effectively prevented against the reductions of tight junctions and the abnormality of intestinal permeability in HG conditions. In conclusion, we confirm the unique alterations of Sdc1 and HPSE in HG conditions, and found their interactions with p38 MAPK activation and IEB. These indicate that Sdc1/HPSE modulation can be viewed as an important complementary treatment for relieving HG-induced gastrointestinal damage.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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