PMID- 32012145
OWN - NLM
STAT- MEDLINE
DCOM- 20201124
LR  - 20201124
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 26
DP  - 2020 Feb 3
TI  - Inhibition of NADPH Oxidase 5 (NOX5) Suppresses High Glucose-Induced Oxidative 
      Stress, Inflammation and Extracellular Matrix Accumulation in Human Glomerular 
      Mesangial Cells.
PG  - e919399
LID - 10.12659/MSM.919399 [doi]
AB  - BACKGROUND The aim of this study was to explore the effects of NADPH oxidase 5 
      (NOX5) in high glucose-stimulated human glomerular mesangial cells (HMCs). 
      MATERIAL AND METHODS Cells were cultured under normal glucose (NG) or high 
      glucose (HG) conditions. Then, NOX5 siRNA was transfected into HG-treated HMCs. A 
      Cell Counting Kit-8 assay, colony formation assay and 5-ethynyl-20-deoxyuridine 
      (EDU) incorporation assay were applied to measure cell proliferative ability. In 
      addition, the levels of oxidative stress factors including reactive oxygen 
      species (ROS), malonaldehyde (MDA), NADPH, superoxide dismutase (SOD), and 
      glutathione peroxidase (GSH-PX), inflammatory cytokines including tumor necrosis 
      factor-alpha (TNF-alpha), interleukin (IL)-6, IL-1ss, and monocyte chemoattractant 
      protein-1 (MCP-1) in HMCs were detected by kits. Moreover, the expression of 
      TLR4/NF-kappaB signaling and extracellular matrix (ECM) associated genes were 
      evaluated by western blotting. RESULTS The results revealed that the NOX5 was 
      overexpressed in HG-treated HMCs. Silencing of NOX5 decreased proliferation of 
      HMCs induced by HG. And NOX5 silencing alleviated the production of MDA and NADPH 
      accompanied by an increase of SOD and GSH-PX levels. Additionally, the contents 
      of TNF-alpha, IL-6, IL-1ss, and MCP-1 were reduced after transfection with NOX5 
      siRNA. Furthermore, silencing of NOX5 deceased the expression of collagen I, 
      collagen IV, TGF-ss1, and fibronectin induced by HG stimulation. TLR4, MyD88, and 
      phospho-NF-kappaB p65 expression were downregulated notably in NOX5 silencing 
      group. CONCLUSIONS Taken together, these findings demonstrated that inhibition of 
      NOX5 attenuated HG-induced HMCs oxidative stress, inflammation, and ECM 
      accumulation, suggesting that NOX5 may serve as a potential therapeutic target 
      for diabetic nephropathy (DN) treatment.
FAU - Li, Yingxin
AU  - Li Y
AD  - Department of Endocrinology, Second Clinical Medical College, Inner Mongolia 
      University for Nationalities (Inner Mongolia Forestry General Hospital), 
      Tongliao, Inner Mongolia, China (mainland).
FAU - Li, Yarong
AU  - Li Y
AD  - Department of Endocrinology, The Centre Hospital of Wuhan, Wuhan, Hubei, China 
      (mainland).
FAU - Zheng, Shouhao
AU  - Zheng S
AD  - Department of Nephrology, Taizhou First People's Hospital, Taizhou, Zhejiang, 
      China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20200203
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 53-59-8 (NADP)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.6.3.- (NADPH Oxidase 5)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Cell Proliferation/drug effects
MH  - Cytokines/metabolism
MH  - Extracellular Matrix/drug effects/*metabolism
MH  - Gene Silencing
MH  - Glucose/*toxicity
MH  - Glutathione Peroxidase/metabolism
MH  - Humans
MH  - Inflammation/*pathology
MH  - Inflammation Mediators/metabolism
MH  - Malondialdehyde/metabolism
MH  - Mesangial Cells/drug effects/*enzymology/*pathology
MH  - NADP/metabolism
MH  - NADPH Oxidase 5/*antagonists & inhibitors/genetics/metabolism
MH  - NF-kappa B/metabolism
MH  - *Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/drug effects
MH  - Superoxide Dismutase/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - Up-Regulation/drug effects/genetics
PMC - PMC7020764
COIS- Conflict of interest None.
EDAT- 2020/02/06 06:00
MHDA- 2020/11/25 06:00
PMCR- 2020/02/03
CRDT- 2020/02/04 06:00
PHST- 2020/02/04 06:00 [entrez]
PHST- 2020/02/06 06:00 [pubmed]
PHST- 2020/11/25 06:00 [medline]
PHST- 2020/02/03 00:00 [pmc-release]
AID - 919399 [pii]
AID - 10.12659/MSM.919399 [doi]
PST - epublish
SO  - Med Sci Monit. 2020 Feb 3;26:e919399. doi: 10.12659/MSM.919399.