PMID- 28054559
OWN - NLM
STAT- MEDLINE
DCOM- 20181102
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
DP  - 2017 Jan 5
TI  - The RhoA/ROCK Pathway Ameliorates Adhesion and Inflammatory Infiltration Induced 
      by AGEs in Glomerular Endothelial Cells.
PG  - 39727
LID - 10.1038/srep39727 [doi]
LID - 39727
AB  - A recent study demonstrated that advanced glycation end products (AGEs) play a 
      role in monocyte infiltration in mesangial areas in diabetic nephropathy. The Ras 
      homolog gene family, member A Rho kinase (RhoA/ROCK) pathway plays a role in 
      regulating cell migration. We hypothesized that the RhoA/ROCK pathway affects 
      adhesion and inflammation in endothelial cells induced by AGEs. Rat glomerular 
      endothelial cells (rGECs) were cultured with AGEs (80 mug/ml) in vitro. The ROCK 
      inhibitor Y27632 (10 nmol/l) and ROCK1-siRNA were used to inhibit ROCK. We 
      investigated levels of the intercellular adhesion molecule 1 (ICAM-1) and 
      monocyte chemoattractant protein1 (MCP-1) in rGECs. Db/db mice were used as a 
      diabetes model and received Fasudil (10 mg/kg/d, n = 6) via intraperitoneal 
      injection for 12 weeks. We found that AGEs increased the expression of ICAM-1 and 
      MCP-1 in rGECs, and the RhoA/ROCK pathway inhibitor Y27632 depressed the release 
      of adhesion molecules. Moreover, blocking the RhoA/ROCK pathway ameliorated 
      macrophage transfer to the endothelium. Reduced expression of adhesion molecules 
      and amelioration of inflammatory cell infiltration in the glomerulus were 
      observed in db/db mice treated with Fasudil. The RhoA/ROCK pathway plays a role 
      in adhesion molecule expression and inflammatory cell infiltration in glomerular 
      endothelial cells induced by AGEs.
FAU - Rao, Jialing
AU  - Rao J
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Ye, Zengchun
AU  - Ye Z
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Tang, Hua
AU  - Tang H
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Wang, Cheng
AU  - Wang C
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Peng, Hui
AU  - Peng H
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Lai, Weiyan
AU  - Lai W
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Li, Yin
AU  - Li Y
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Huang, Wanbing
AU  - Huang W
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
FAU - Lou, Tanqi
AU  - Lou T
AD  - Division of Nephrology, Department of Medicine, The Third Affiliated Hospital of 
      Sun Yet-sen University, Guangzhou, Guangdong 510630, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170105
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Amides)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Small Interfering)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 138381-45-0 (Y 27632)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - EC 2.7.11.1 (ROCK1 protein, rat)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
RN  - Q0CH43PGXS (fasudil)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/therapeutic 
      use
MH  - Amides/pharmacology
MH  - Animals
MH  - Cell Adhesion
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Diabetic Nephropathies/drug therapy/immunology/*metabolism
MH  - Disease Models, Animal
MH  - Endothelial Cells/*physiology
MH  - Glycation End Products, Advanced/metabolism
MH  - Inflammation/drug therapy/immunology/*metabolism
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Kidney Glomerulus/*pathology
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Pyridines/pharmacology
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Signal Transduction
MH  - rho-Associated Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - rhoA GTP-Binding Protein/*metabolism
PMC - PMC5215591
EDAT- 2017/01/06 06:00
MHDA- 2018/11/06 06:00
PMCR- 2017/01/05
CRDT- 2017/01/06 06:00
PHST- 2015/10/29 00:00 [received]
PHST- 2016/11/28 00:00 [accepted]
PHST- 2017/01/06 06:00 [entrez]
PHST- 2017/01/06 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2017/01/05 00:00 [pmc-release]
AID - srep39727 [pii]
AID - 10.1038/srep39727 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jan 5;7:39727. doi: 10.1038/srep39727.