PMID- 25533544 OWN - NLM STAT- MEDLINE DCOM- 20150521 LR - 20171116 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 98 IP - 1 DP - 2015 Feb TI - Vacuolar protein sorting 4B regulates apoptosis of intestinal epithelial cells via p38 MAPK in Crohn's disease. PG - 55-64 LID - S0014-4800(14)00204-4 [pii] LID - 10.1016/j.yexmp.2014.12.007 [doi] AB - Vacuolar protein sorting 4B (VPS4B), a member of ATPase family proteins, reportedly possesses multiple biological functions, such as regulating the development of breast cancer and non-small-cell lung cancer, participating in Parkinson's disease, and modulating neuronal apoptosis after cerebral ischemia. However, its expression and potential functions in Crohn's disease (CD) has not been understood. In this study, we reported for the first time that VPS4B was over-expressed in intestinal epithelial cell (IECs) of patients with CD. In TNBS-induced mouse colitis models, we observed the up-regulation of VPS4B was accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and phosphorylated p38 in colitis IECs. Co-localization of VPS4B and active caspase-3 in IECs of the TNBS group further indicated the possible involvement of VPS4B in IEC apoptosis. Employing the TNF-alpha-treated HT29 cells as an in vitro IEC apoptosis model, we confirmed the positive correlation of VPS4B with caspase-dependent cellular apoptosis. Knocking VPS4B down by siRNA significantly alleviated TNF-alpha-induced p38 phosphorylation and cellular apoptosis in HT29 cells. Taken together, our findings suggested that VPS4B may facilitate the IEC apoptosis in CD via p38 MAPK signaling pathway. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Zhang, Dongmei AU - Zhang D AD - Department of Pathogen Biology, Medical College, Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province, People's Republic of China. FAU - Wang, Liang AU - Wang L AD - Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. FAU - Yan, Lijun AU - Yan L AD - Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210000, Jiangsu Province, People's Republic of China. FAU - Miao, Xianjing AU - Miao X AD - Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. FAU - Gong, Chen AU - Gong C AD - Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. FAU - Xiao, Min AU - Xiao M AD - National Glycoengineering Research Center, State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, People's Republic of China. FAU - Ni, Runzhou AU - Ni R AD - Department of Gastroenterology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province, People's Republic of China. FAU - Tang, Qiyun AU - Tang Q AD - Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210000, Jiangsu Province, People's Republic of China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141220 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Endosomal Sorting Complexes Required for Transport) RN - 0 (RNA, Small Interfering) RN - 0 (Tumor Necrosis Factor-alpha) RN - 8T3HQG2ZC4 (Trinitrobenzenesulfonic Acid) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.6.1.- (Adenosine Triphosphatases) RN - EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities) RN - EC 3.6.4.6 (VPS4B protein, human) SB - IM MH - ATPases Associated with Diverse Cellular Activities MH - Adenosine Triphosphatases/antagonists & inhibitors/genetics/*metabolism MH - Animals MH - *Apoptosis MH - Blotting, Western MH - Caspase 3/metabolism MH - Cell Proliferation MH - Colitis/chemically induced/metabolism/pathology MH - Crohn Disease/drug therapy/metabolism/*pathology MH - Endosomal Sorting Complexes Required for Transport/antagonists & inhibitors/genetics/*metabolism MH - Epithelial Cells/drug effects/metabolism/*pathology MH - Female MH - HT29 Cells MH - Humans MH - Immunoenzyme Techniques MH - Intestinal Mucosa/drug effects/metabolism/*pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - RNA, Small Interfering/genetics MH - Signal Transduction MH - Trinitrobenzenesulfonic Acid/toxicity MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/pharmacology MH - p38 Mitogen-Activated Protein Kinases/*metabolism OTO - NOTNLM OT - Apoptosis OT - Crohn's disease OT - Intestinal epithelial cell OT - Phosphorylated p38 OT - VPS4B EDAT- 2014/12/24 06:00 MHDA- 2015/05/23 06:00 CRDT- 2014/12/24 06:00 PHST- 2014/12/15 00:00 [received] PHST- 2014/12/18 00:00 [accepted] PHST- 2014/12/24 06:00 [entrez] PHST- 2014/12/24 06:00 [pubmed] PHST- 2015/05/23 06:00 [medline] AID - S0014-4800(14)00204-4 [pii] AID - 10.1016/j.yexmp.2014.12.007 [doi] PST - ppublish SO - Exp Mol Pathol. 2015 Feb;98(1):55-64. doi: 10.1016/j.yexmp.2014.12.007. Epub 2014 Dec 20.