PMID- 35224007
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220502
IS  - 2296-9381 (Print)
IS  - 2296-9357 (Electronic)
IS  - 2296-9357 (Linking)
VI  - 8
IP  - 1
DP  - 2022 Jan
TI  - Targeting Ferroptosis Attenuates Interstitial Inflammation and Kidney Fibrosis.
PG  - 57-71
LID - 10.1159/000517723 [doi]
AB  - BACKGROUND: Ferroptosis, an iron-dependent form of regulated necrosis mediated by 
      lipid peroxidation, predominantly polyunsaturated fatty acids, is involved in 
      postischemic and toxic kidney injury. However, the role and mechanisms for 
      tubular epithelial cell (TEC) ferroptosis in kidney fibrosis remain largely 
      unknown. OBJECTIVES: The aim of the study was to decipher the role and mechanisms 
      for TEC ferroptosis in kidney fibrosis. METHODS: Mouse models with unilateral 
      ureter obstruction (UUO) or ischemia/reperfusion injury (IRI) were generated. 
      RESULTS: We found that TEC ferroptosis exhibited as reduced glutathione 
      peroxidase 4 (GPX4) expression and increased 4-hydroxynonenal abundance was 
      appeared in kidneys from chronic kidney disease (CKD) patients and mouse models 
      with UUO or IRI. Inhibition of ferroptosis could largely mitigate kidney injury, 
      interstitial fibrosis, and inflammatory cell accumulation in mice after UUO or 
      IRI. Additionally, treatment of TECs with (1S,3R)-RSL-3, an inhibitor of GPX4, 
      could enhance cell ferroptosis and recruit macrophages. Furthermore, inhibiting 
      TEC ferroptosis reduced monocyte chemotactic protein 1 (MCP-1) secretion and 
      macrophage chemotaxis. CONCLUSIONS: This study uncovers that TEC ferroptosis may 
      promote interstitial fibrosis and inflammation, and targeting ferroptosis may 
      shine a light on protecting against kidney fibrosis in patients with CKDs.
CI  - Copyright (c) 2021 by S. Karger AG, Basel.
FAU - Zhou, Lu
AU  - Zhou L
AD  - Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Xue, Xian
AU  - Xue X
AD  - Department of Clinical Genetics, The Second Affiliated Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Hou, Qing
AU  - Hou Q
AD  - Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical 
      University, Nanjing, China.
FAU - Dai, Chunsun
AU  - Dai C
AD  - Center for Kidney Disease, The Second Affiliated Hospital, Nanjing Medical 
      University, Nanjing, China.
AD  - Department of Clinical Genetics, The Second Affiliated Hospital, Nanjing Medical 
      University, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20210803
PL  - Switzerland
TA  - Kidney Dis (Basel)
JT  - Kidney diseases (Basel, Switzerland)
JID - 101658365
PMC - PMC8820137
OTO - NOTNLM
OT  - Ferroptosis
OT  - Kidney fibrosis
OT  - Tubular cells
COIS- Chunsun Dai is Associate Editor of the journal of "Kidney Diseases." The authors 
      declare that they have no conflicts of interest with the contents of this 
      article.
EDAT- 2022/03/01 06:00
MHDA- 2022/03/01 06:01
PMCR- 2021/08/03
CRDT- 2022/02/28 05:40
PHST- 2020/11/19 00:00 [received]
PHST- 2021/06/08 00:00 [accepted]
PHST- 2022/02/28 05:40 [entrez]
PHST- 2022/03/01 06:00 [pubmed]
PHST- 2022/03/01 06:01 [medline]
PHST- 2021/08/03 00:00 [pmc-release]
AID - kdd-0008-0057 [pii]
AID - 10.1159/000517723 [doi]
PST - epublish
SO  - Kidney Dis (Basel). 2021 Aug 3;8(1):57-71. doi: 10.1159/000517723. eCollection 
      2022 Jan.