Downregulation of exocyst Sec10 accelerates kidney tubule cell recovery through enhanced cell migration

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 investigate...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2018-02, Vol.496 (2), p.309-315
Main Authors: Noh, Mi Ra, Jang, Hee-Seong, Song, Dae-Kyu, Lee, Seong-Ryong, Lipschutz, Joshua H., Park, Kwon Moo, Kim, Jee In
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
CELL CULTURES
DGK gamma
Exocyst Sec10
HEALING
ISCHEMIA
Kidney tubule cell
MICE
Migration
PHOSPHOTRANSFERASES
Ruffle formation
Wound healing
WOUNDS
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. •Exocyst Sec10 decreases by I/R injury and restores with functional recovery.•Sec10 inversely regulates kidney tubule cell wound healing after scratch injury.•Sec10 inversely regulates ruffle formation at the leading edge during recovery.•Upregulation of Sec10 increases DGKγ expression at the leading edge during recovery.•DGK inhibitor reversed Sec10-mediated ruffle formation and wound healing defect.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2018.01.013