PMID- 37833977
OWN - NLM
STAT- MEDLINE
DCOM- 20231115
LR  - 20231115
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 19
DP  - 2023 Sep 26
TI  - Kruppel-like Factor 15 Suppresses Ferroptosis by Activating an NRF2/GPX4 Signal 
      to Protect against Folic Acid-Induced Acute Kidney Injury.
LID - 10.3390/ijms241914530 [doi]
LID - 14530
AB  - Acute kidney injury (AKI) is a common and serious disease with high morbidity and 
      mortality, and its pathophysiological mechanisms are not fully understood. 
      Increasing evidence suggests an important role of ferroptosis in AKI. 
      Kruppel-like factor 15 (KLF15) is a transcription factor involved in several 
      metabolic diseases, but its role in AKI and ferroptosis remains unclear. In this 
      study, we explored the potential role of KLF15 using a folic acid-induced AKI 
      model. Our study showed that KLF15 expression was reduced in kidney tissues of 
      AKI mice, and KLF15 knockout exacerbated folic acid-induced ferroptosis and 
      kidney injury. In vitro studies revealed that the ferroptosis inducer erastin 
      significantly suppressed KLF15 expression in human tubular epithelial cells. 
      Notably, the overexpression of KLF15 attenuated ferroptosis, as evidenced by a 
      decrease in the lipid peroxidation marker of malondialdehyde and the upregulation 
      of glutathione peroxidase 4 (GPX4), while KLF15 knockdown with shRNA exerted the 
      opposite effect. Mechanistically, KLF15 stabilized the protein of nuclear factor 
      erythroid 2-related factor 2 (NRF2) and subsequently increased the GPX4 level. 
      Collectively, KLF15 plays an important role in the modulation of ferroptosis in 
      AKI and may be a potential therapeutic target for treating AKI.
FAU - Yang, Xue
AU  - Yang X
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Dong, Shihui
AU  - Dong S
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Fan, Yun
AU  - Fan Y
AD  - Jinling Clinical Medical College, Nanjing Medical University, Nanjing 210008, 
      China.
FAU - Xia, Yuanyuan
AU  - Xia Y
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Yang, Fan
AU  - Yang F
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Chen, Zhaohong
AU  - Chen Z
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Chen, Dacheng
AU  - Chen D
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Zhang, Mingchao
AU  - Zhang M
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Liang, Dandan
AU  - Liang D
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
FAU - Zeng, Caihong
AU  - Zeng C
AUID- ORCID: 0000-0002-3816-5164
AD  - National Clinical Research Center for Kidney Diseases, Jinling Hospital, 
      Affiliated Hospital of Medical School, Nanjing University, Nanjing 210044, China.
LA  - eng
GR  - 82070793/the National Natural Science Foundation of China/
GR  - ZD2021018/the Key Program of Health Commission Foundation of Jiangsu Province/
PT  - Journal Article
DEP - 20230926
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 935E97BOY8 (Folic Acid)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (NF-E2-Related Factor 2)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Acute Kidney Injury/chemically induced/genetics/prevention & control
MH  - *Ferroptosis
MH  - Folic Acid/pharmacology
MH  - *Kruppel-Like Transcription Factors/genetics
MH  - NF-E2-Related Factor 2/genetics
PMC - PMC10572468
OTO - NOTNLM
OT  - GPX4
OT  - KLF15
OT  - NRF2
OT  - acute kidney injury
OT  - ferroptosis
COIS- The authors declare no conflict of interest.
EDAT- 2023/10/14 10:49
MHDA- 2023/11/01 12:43
PMCR- 2023/09/26
CRDT- 2023/10/14 01:01
PHST- 2023/08/08 00:00 [received]
PHST- 2023/09/16 00:00 [revised]
PHST- 2023/09/23 00:00 [accepted]
PHST- 2023/11/01 12:43 [medline]
PHST- 2023/10/14 10:49 [pubmed]
PHST- 2023/10/14 01:01 [entrez]
PHST- 2023/09/26 00:00 [pmc-release]
AID - ijms241914530 [pii]
AID - ijms-24-14530 [pii]
AID - 10.3390/ijms241914530 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Sep 26;24(19):14530. doi: 10.3390/ijms241914530.