PMID- 35441585
OWN - NLM
STAT- MEDLINE
DCOM- 20220421
LR  - 20220716
IS  - 2165-5987 (Electronic)
IS  - 2165-5979 (Print)
IS  - 2165-5979 (Linking)
VI  - 13
IP  - 4
DP  - 2022 Apr
TI  - The protective effects of cabozantinib against high glucose-induced damages in in 
      vitro renal glomerular endothelial cells model via inhibition of early growth 
      response-1 (Egr-1).
PG  - 10605-10616
LID - 10.1080/21655979.2022.2063667 [doi]
AB  - Cabozantinib is a tyrosine kinase inhibitor with anti-tumor activity in kidney 
      cancer. However, the efficacy of cabozantinib in other renal diseases has never 
      been reported. Here, we focused on exploring the effect of cabozantinib on 
      diabetic nephropathy (DN). The biofunctions of cabozantinib in human renal 
      glomerular endothelial cells (hGECs) under high glucose conditions have been 
      investigated. We found that cabozantinib ameliorated high glucose-induced 
      oxidative stress in hGECs with decreased production of mitochondrial reactive 
      oxygen species (ROS) and increased glutathione peroxidase (GSH-PX) activity. 
      Cabozantinib ameliorated high glucose-induced reduction in the expression of 
      endothelial nitric oxide synthase (eNOS) and the production of nitric oxide (NO) 
      in hGECs. It also suppressed the expression of pro-inflammatory mediators, 
      interleukin-6 (IL-6) and monocyte chemokine protein 1 (MCP-1), against high 
      glucose exposure in hGECs. Cabozantinib reduced the expression of early growth 
      response-1 (Egr-1) in high glucose-treated hGECs, while Egr-1 overexpression 
      abolished the protective effects of cabozantinib against high glucose in hGECs. 
      In conclusion, cabozantinib protected hGECs from high glucose-induced oxidative 
      stress, NO deficiency, and inflammation via regulating Egr-1. These findings 
      suggest that cabozantinib might be used as an adjuvant to control DN.
FAU - Ye, Hanlu
AU  - Ye H
AD  - Department of Endocrine and Metabolic Diseases, Wuhan Hospital of Traditional 
      Chinese Medicine, Wuhan City, Hubei Province, China.
FAU - Yan, Jingjing
AU  - Yan J
AD  - Respiratory Department Attending Surgeon, Wuhan Hospital of Traditional Chinese 
      Medicine, Wuhan City, Hubei Province, China.
FAU - Wang, Qiong
AU  - Wang Q
AD  - Department of Endocrine and Metabolic Diseases, Wuhan Hospital of Traditional 
      Chinese Medicine, Wuhan City, Hubei Province, China.
FAU - Tian, Hui
AU  - Tian H
AD  - Respiratory Department Attending Surgeon, Wuhan Hospital of Traditional Chinese 
      Medicine, Wuhan City, Hubei Province, China.
FAU - Zhou, Lei
AU  - Zhou L
AD  - Nephrology Department Attending Surgeon, Wuhan Hospital of Traditional Chinese 
      Medicine, Wuhan City, Hubei Province, China.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Bioengineered
JT  - Bioengineered
JID - 101581063
RN  - 0 (Anilides)
RN  - 0 (Antioxidants)
RN  - 0 (Pyridines)
RN  - 1C39JW444G (cabozantinib)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Anilides/metabolism/pharmacology
MH  - Antioxidants
MH  - *Diabetic Nephropathies/drug therapy/metabolism/pathology
MH  - *Endothelial Cells/metabolism
MH  - Female
MH  - Glucose/metabolism
MH  - Humans
MH  - Male
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress
MH  - Pyridines
PMC - PMC9161968
OTO - NOTNLM
OT  - Cabozantinib
OT  - Egr-1
OT  - diabetic nephropathy (DN)
OT  - high glucose
OT  - human renal glomerular endothelial cells (hGECs)
OT  - oxidative stress
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/04/21 06:00
MHDA- 2022/04/22 06:00
PMCR- 2022/04/20
CRDT- 2022/04/20 08:41
PHST- 2022/04/20 08:41 [entrez]
PHST- 2022/04/21 06:00 [pubmed]
PHST- 2022/04/22 06:00 [medline]
PHST- 2022/04/20 00:00 [pmc-release]
AID - 2063667 [pii]
AID - 10.1080/21655979.2022.2063667 [doi]
PST - ppublish
SO  - Bioengineered. 2022 Apr;13(4):10605-10616. doi: 10.1080/21655979.2022.2063667.