PMID- 37760019
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231003
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 9
DP  - 2023 Sep 4
TI  - NRF2 Deficiency Attenuates Diabetic Kidney Disease in Db/Db Mice via 
      Down-Regulation of Angiotensinogen, SGLT2, CD36, and FABP4 Expression and Lipid 
      Accumulation in Renal Proximal Tubular Cells.
LID - 10.3390/antiox12091715 [doi]
LID - 1715
AB  - The role(s) of nuclear factor erythroid 2-related factor 2 (NRF2) in diabetic 
      kidney disease (DKD) is/are controversial. We hypothesized that Nrf2 deficiency 
      in type 2 diabetes (T2D) db/db mice (db/dbNrf2 knockout (KO)) attenuates DKD 
      progression through the down-regulation of angiotensinogen (AGT), sodium-glucose 
      cotransporter-2 (SGLT2), scavenger receptor CD36, and fatty -acid-binding protein 
      4 (FABP4), and lipid accumulation in renal proximal tubular cells (RPTCs). 
      Db/dbNrf2 KO mice were studied at 16 weeks of age. Human RPTCs (HK2) with NRF2 KO 
      via CRISPR-Cas9 genome editing and kidneys from patients with or without T2D were 
      examined. Compared with db/db mice, db/dbNrf2 KO mice had lower systolic blood 
      pressure, fasting blood glucose, kidney hypertrophy, glomerular filtration rate, 
      urinary albumin/creatinine ratio, tubular lipid droplet accumulation, and 
      decreased expression of AGT, SGLT2, CD36, and FABP4 in RPTCs. Male and female 
      mice had similar results. NRF2 KO attenuated the stimulatory effect of the Nrf2 
      activator, oltipraz, on AGT, SGLT2, and CD36 expression and high-glucose/free 
      fatty acid (FFA)-stimulated lipid accumulation in HK2. Kidneys from T2D patients 
      exhibited markedly higher levels of CD36 and FABP4 in RPTCs than kidneys from 
      non-diabetic patients. These data suggest that NRF2 exacerbates DKD through the 
      stimulation of AGT, SGLT2, CD36, and FABP4 expression and lipid accumulation in 
      RPTCs of T2D.
FAU - Su, Ke
AU  - Su K
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Zhao, Shui-Ling
AU  - Zhao SL
AUID- ORCID: 0000-0002-0769-5365
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Yang, Wen-Xia
AU  - Yang WX
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Lo, Chao-Sheng
AU  - Lo CS
AUID- ORCID: 0000-0003-0645-7987
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Chenier, Isabelle
AU  - Chenier I
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Liao, Min-Chun
AU  - Liao MC
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Pang, Yu-Chao
AU  - Pang YC
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Peng, Jun-Zheng
AU  - Peng JZ
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Miyata, Kana N
AU  - Miyata KN
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Cailhier, Jean-Francois
AU  - Cailhier JF
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Ethier, Jean
AU  - Ethier J
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Lattouf, Jean-Baptiste
AU  - Lattouf JB
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Filep, Janos G
AU  - Filep JG
AUID- ORCID: 0000-0001-5022-3534
AD  - Centre de Recherche, Hopital Maisonneuve-Rosemont, Departement de Pathologie et 
      Biologie Cellulaire, Universite de Montreal, 5415 Boul. de l'Assomption, 
      Montreal, QC H1T 2M4, Canada.
FAU - Ingelfinger, Julie R
AU  - Ingelfinger JR
AD  - Pediatric Nephrology Unit, Massachusetts General Hospital, Harvard Medical 
      School, 15 Parkman Street, WAC 709, Boston, MA 02114, USA.
FAU - Zhang, Shao-Ling
AU  - Zhang SL
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
FAU - Chan, John S D
AU  - Chan JSD
AUID- ORCID: 0000-0002-7137-454X
AD  - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), 
      Departement de Medecine, Universite de Montreal, 900 Saint Denis Street, 
      Montreal, QC H2X 0A9, Canada.
LA  - eng
GR  - PJT-186199/CAPMC/CIHR/Canada
PT  - Journal Article
DEP - 20230904
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC10525648
OTO - NOTNLM
OT  - CD36
OT  - NRF2
OT  - SGLT2
COIS- The authors declare no conflict of interest.
EDAT- 2023/09/28 06:42
MHDA- 2023/09/28 06:43
PMCR- 2023/09/04
CRDT- 2023/09/28 01:04
PHST- 2023/06/30 00:00 [received]
PHST- 2023/08/17 00:00 [revised]
PHST- 2023/08/28 00:00 [accepted]
PHST- 2023/09/28 06:43 [medline]
PHST- 2023/09/28 06:42 [pubmed]
PHST- 2023/09/28 01:04 [entrez]
PHST- 2023/09/04 00:00 [pmc-release]
AID - antiox12091715 [pii]
AID - antioxidants-12-01715 [pii]
AID - 10.3390/antiox12091715 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 Sep 4;12(9):1715. doi: 10.3390/antiox12091715.