title: High glucose-induced intestinal epithelial barrier damage is aggravated by syndecan-1 destruction and heparanase overexpression.
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.
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.|Department of Gastroenterology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Qing
authors.affiliation: Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shaoheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangdong Provincial Key Laboratory of Gastroenterology, Guangzhou, China.
authors.forename: Runhua
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Mao
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Qikui
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D017097:Electric Impedance; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007422:Intestines / Q000166:cytology; D051379:Mice; D008856:Microscopy, Fluorescence; D062793:Occludin / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1 / Q000235:genetics* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099175:Heparanase
chemical_list: D005947:Glucose; D005966:Glucuronidase; D007004:Hypoglycemic Agents; D007328:Insulin; D062793:Occludin; D053668:Syndecan-1; D062826:Zonula Occludens-1 Protein; D048051:p38 Mitogen-Activated Protein Kinases; D000099175:Heparanase
keywords: diabetes; heparanase; high glucose; intestinal epithelial barrier; syndecan-1