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

Author:
Noh, Mi Ra, Jang, Hee-Seong, Song, Dae-Kyu, Lee, Seong-Ryong, Lipschutz, Joshua H., Park, Kwon Moo, Kim, Jee In
Source:
Biochemical and biophysical research communications 2018 v.496 no.2 pp. 309-315
ISSN:
0006-291X
Subject:
cell culture, cell movement, diacylglycerol kinase, dogs, exocytosis, ischemia, kidneys, mice, tissue repair
Abstract:
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.
Agid:
6280244