PMID- 29326040 OWN - NLM STAT- MEDLINE DCOM- 20180214 LR - 20180214 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 496 IP - 2 DP - 2018 Feb 5 TI - Downregulation of exocyst Sec10 accelerates kidney tubule cell recovery through enhanced cell migration. PG - 309-315 LID - S0006-291X(18)30013-5 [pii] LID - 10.1016/j.bbrc.2018.01.013 [doi] AB - Migration of surviving kidney tubule cells after sub-lethal injury, for example ischemia/reperfusion (I/R), plays a critical role in recovery. Exocytosis is known to be involved in cell migration, and a key component in exocytosis is the highly-conserved eight-protein exocyst complex. We investigated the expression of a central exocyst complex member, Sec10, in kidneys following I/R injury, as well as the role of Sec10 in wound healing following scratch injury of cultured Madin-Darby canine kidney (MDCK) cells. Sec10 overexpression and knockdown (KD) in MDCK cells were used to investigate the speed of wound healing and the mechanisms underlying recovery. In mice, Sec10 decreased after I/R injury, and increased during the recovery period. In cell culture, Sec10 OE inhibited ruffle formation and wound healing, while Sec10 KD accelerated it. Sec10 OE cells had higher amounts of diacylglycerol kinase (DGK) gamma at the leading edge than did control cells. A DGK inhibitor reversed the inhibition of wound healing and ruffle formation in Sec10 OE cells. Conclusively, downregulation of Sec10 following I/R injury appears to accelerate recovery of kidney tubule cells through activated ruffle formation and enhanced cell migration. CI - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Noh, Mi Ra AU - Noh MR AD - Department of Anatomy and BK21 Plus, Kyungpook National University School of Medicine, Daegu, Republic of Korea. FAU - Jang, Hee-Seong AU - Jang HS AD - Department of Anatomy and BK21 Plus, Kyungpook National University School of Medicine, Daegu, Republic of Korea. FAU - Song, Dae-Kyu AU - Song DK AD - Department of Physiology, Keimyung University School of Medicine, Daegu, Republic of Korea; Medical Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea. FAU - Lee, Seong-Ryong AU - Lee SR AD - Medical Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea; Department of Pharmacology, Keimyung University School of Medicine, Daegu, Republic of Korea. FAU - Lipschutz, Joshua H AU - Lipschutz JH AD - Department of Medicine, Medical University of South Carolina and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA. FAU - Park, Kwon Moo AU - Park KM AD - Department of Anatomy and BK21 Plus, Kyungpook National University School of Medicine, Daegu, Republic of Korea. Electronic address: kmpark@knu.ac.kr. FAU - Kim, Jee In AU - Kim JI AD - Medical Research Center, Keimyung University School of Medicine, Daegu, Republic of Korea; Department of Molecular Medicine Keimyung University School of Medicine, Daegu, Republic of Korea. Electronic address: jeein.kim@kmu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180108 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (EXOC5 protein, mouse) RN - 0 (Enzyme Inhibitors) RN - 0 (Piperidines) RN - 0 (Quinazolinones) RN - 0 (RNA, Small Interfering) RN - 0 (Vesicular Transport Proteins) RN - 120166-69-0 (R 59949) RN - EC 2.7.1.107 (Diacylglycerol Kinase) SB - IM MH - Animals MH - Biological Assay MH - Cell Line MH - Cell Movement/drug effects MH - Diacylglycerol Kinase/*antagonists & inhibitors/genetics/metabolism MH - Dogs MH - Enzyme Inhibitors/pharmacology MH - Exocytosis MH - Gene Expression Regulation MH - Kidney Tubules/*metabolism/pathology MH - Madin Darby Canine Kidney Cells MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Piperidines/pharmacology MH - Quinazolinones/pharmacology MH - RNA, Small Interfering/genetics/metabolism MH - Reperfusion Injury/genetics/metabolism/pathology/*prevention & control MH - Vesicular Transport Proteins/agonists/antagonists & inhibitors/*genetics/metabolism MH - Wound Healing/physiology OTO - NOTNLM OT - DGK gamma OT - Exocyst Sec10 OT - Kidney tubule cell OT - Migration OT - Ruffle formation OT - Wound healing EDAT- 2018/01/13 06:00 MHDA- 2018/02/15 06:00 CRDT- 2018/01/13 06:00 PHST- 2017/12/22 00:00 [received] PHST- 2018/01/03 00:00 [accepted] PHST- 2018/01/13 06:00 [pubmed] PHST- 2018/02/15 06:00 [medline] PHST- 2018/01/13 06:00 [entrez] AID - S0006-291X(18)30013-5 [pii] AID - 10.1016/j.bbrc.2018.01.013 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Feb 5;496(2):309-315. doi: 10.1016/j.bbrc.2018.01.013. Epub 2018 Jan 8.