PMID- 28542370
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 5
DP  - 2017
TI  - Upregulation of TLR4 via PKC activation contributes to impaired wound healing in 
      high-glucose-treated kidney proximal tubular cells.
PG  - e0178147
LID - 10.1371/journal.pone.0178147 [doi]
LID - e0178147
AB  - Acute kidney injury (AKI) leads to a worse prognosis in diabetic patients 
      compared with prognoses in non-diabetic patients, but whether and how diabetes 
      affects kidney repair after AKI remains unknown. Here, we used scratch-wound 
      healing and transwell migration models to examine whether and how wound healing 
      is affected by high glucose levels in cultured kidney proximal tubular cells 
      (RPTC). The results show that scratch-wound healing and transwell migration were 
      significantly slower in high-glucose-treated kidney tubular cells (30 mM glucose) 
      than in low-glucose-treated cells (5.5 mM). Toll-like receptor 4 (TLR4), MyD88, 
      phospho-protein kinase C (PKC), phospho-p38 MAPK and monocyte chemoattractant 
      protein-1 (MCP-1) mRNA levels were upregulated after high glucose treatments. 
      Staurosporine, a selective PKC inhibitor, inhibited TLR4, MyD88 and p-p38 
      upregulation in the high-glucose-treated cells, indicating the involvement of PKC 
      in high-glucose-induced TLR4 upregulation. The pharmacological inhibition of TLR4 
      or shRNA-mediated TLR4 knockdown improved wound healing and transwell migration 
      in high-glucose-treated RPTC. In contrast, the overexpression of TLR4 in 
      low-glucose-treated RPTC suppressed wound healing, mimicking the effects of high 
      glucose levels. These results suggest that the upregulation of TLR4 expression 
      via PKC activation contributes to defective wound healing in high-glucose-treated 
      kidney tubular cells.
FAU - Peng, Jianping
AU  - Peng J
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
FAU - Zheng, Hang
AU  - Zheng H
AD  - Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
FAU - Wang, Xia
AU  - Wang X
AD  - Department of Internal Medicine, Hospital of Wuhan University, Wuhan University, 
      Wuhan, China.
FAU - Cheng, Zhixiang
AU  - Cheng Z
AD  - Department of General Surgery, Zhongnan Hospital of Wuhan University, Wuhan 
      University, Wuhan, China.
LA  - eng
PT  - Journal Article
DEP - 20170524
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (RNA, Messenger)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Movement/drug effects/physiology
MH  - Cells, Cultured
MH  - Gene Knockdown Techniques
MH  - Glucose/*metabolism/pharmacology
MH  - HEK293 Cells
MH  - Humans
MH  - Kidney Tubules, Proximal/cytology/drug effects/*metabolism
MH  - Protein Kinase C/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Toll-Like Receptor 4/antagonists & inhibitors/genetics/*metabolism
MH  - Up-Regulation
MH  - Wound Healing/drug effects/genetics/*physiology
PMC - PMC5443579
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/05/26 06:00
MHDA- 2017/09/19 06:00
PMCR- 2017/05/24
CRDT- 2017/05/26 06:00
PHST- 2016/06/14 00:00 [received]
PHST- 2017/05/09 00:00 [accepted]
PHST- 2017/05/26 06:00 [entrez]
PHST- 2017/05/26 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2017/05/24 00:00 [pmc-release]
AID - PONE-D-16-22575 [pii]
AID - 10.1371/journal.pone.0178147 [doi]
PST - epublish
SO  - PLoS One. 2017 May 24;12(5):e0178147. doi: 10.1371/journal.pone.0178147. 
      eCollection 2017.