title: Suppressing Syndecan-1 Shedding Ameliorates Intestinal Epithelial Inflammation through Inhibiting NF-κB Pathway and TNF-α.
abstract: Syndecan-1 (SDC1), with a long variable ectodomain carrying heparan sulfate chains, participates in many steps of inflammatory responses. But reports about the efforts of SDC1's unshedding ectodomain on intestinal epithelial inflammation and the precise underlying mechanism are limited. In our study, unshedding SDC1 from intestinal epithelial cell models was established by transfecting with unshedding SDC1 plasmid into the cell, respectively. And the role of unshedding SDC1 in intestinal inflammation was further investigated. We found that components of NF-κB pathway, including P65 and IκBα, and secretion of TNF-α were upregulated upon LPS stimulation in intestinal epithelial cells. SDC1, especially through its unshed ectodomain, significantly lessened the upregulation extent. It also functioned in inhibiting migration of neutrophils by downregulating secretion of CXCL-1. Taken together, we conclude that suppressing SDC1 shedding from intestinal epithelial cells relieves severity of intestinal inflammation by inactivating NF-κB pathway and downregulating TNF-α expression. These results indicate that the ectodomain of SDC1 might be the optional therapy for intestinal inflammation.
authors: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, Guangdong 510515, China; Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China.
authors: Yan
authors: Y
authors: Zhang
authors: Department of Radiation Oncology and Cyberknife Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China.
authors: Zhongqiu
authors: Z
authors: Wang
authors: Department of Gastroenterology, Liuzhou Worker's Hospital, Liuzhou 545005, China.
authors: Jun
authors: J
authors: Liu
authors: Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China.
authors: Zhenyu
authors: Z
authors: Zhang
authors: State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Road, Guangzhou, Guangdong 510515, China.
authors: Ye
authors: 0000-0001-6556-9861
authors: Y
authors: Chen