PMID- 37123216
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230502
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Print)
IS  - 1792-0981 (Linking)
VI  - 25
IP  - 5
DP  - 2023 May
TI  - Heme oxygenase‑1 inhibits renal tubular epithelial cell pyroptosis by regulating 
      mitochondrial function through PINK1.
PG  - 213
LID - 10.3892/etm.2023.11912 [doi]
LID - 213
AB  - Endotoxin-induced acute kidney injury (AKI) is commonly observed in clinical 
      practice. Renal tubular epithelial cell (RTEC) pyroptosis is one of the main 
      factors leading to the development of endotoxin-induced AKI. Mitochondrial 
      dysfunction can lead to pyroptosis. However, the biological pathways involved in 
      the potential lipopolysaccharide (LPS)-induced pyroptosis of RTECs, notably those 
      associated with mitochondrial dysfunction, are poorly understood. Previous 
      studies have demonstrated that heme oxygenase (HO)-1 confers cell protection via 
      the induction of PTEN-induced putative kinase 1 (PINK1) expression through PTEN 
      to regulate mitochondrial fusion/fission during endotoxin-induced AKI in vivo. 
      Therefore, the present study investigated the role of HO-1/PINK1 in maintaining 
      mitochondrial function and inhibiting the pyroptosis of RTECs exposed to LPS. 
      Primary cultures of RTECs were obtained from wild-type (WT) and PINK1-knockout 
      (PINK1KO) rats. An in vitro model of endotoxin-associated RTEC injury was 
      established following treatment of the cells with LPS. The WT RTECs were divided 
      into the control, LPS, Znpp + LPS and Hemin + LPS groups, and the PINK1KO RTECs 
      were divided into the control, LPS and Hemin + LPS groups. RTECs were exposed to 
      LPS for 6 h to assess cell viability, inflammation, pyroptosis and mitochondrial 
      function. In the LPS-treated RTECs, the mRNA and protein expression levels of 
      HO-1 and PINK1 were upregulated. Cell viability, adenosine triphosphate (ATP) 
      levels and the mitochondrial oxygen consumption rate were decreased, whereas the 
      inflammatory response, pyroptosis and mitochondrial reactive oxygen species (ROS) 
      levels were increased. The cell inflammatory response and the induction of 
      pyroptosis were inhibited, whereas the levels of mitochondrial ROS were 
      decreased. In addition, the cell viability and ATP levels were increased in the 
      WT RTECs following the upregulation of HO-1 expression. These effects were 
      reversed by the downregulation of HO-1 expression. However, no statistically 
      significant differences were noted between the LPS and the Hemin + LPS groups in 
      the PINK1KO RTECs. Collectively, the findings of the present study indicate that 
      HO-1 inhibits inflammation and regulates mitochondrial function by inhibiting the 
      pyroptosis of LPS-exposed RTECs via PINK1.
CI  - Copyright: (c) Li et al.
FAU - Li, Hai-Bo
AU  - Li HB
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Mo, Yan-Shuai
AU  - Mo YS
AD  - Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, 
      Tianjin Medical University, Tianjin 300102, P.R. China.
FAU - Zhang, Xi-Zhe
AU  - Zhang XZ
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Zhou, Qi
AU  - Zhou Q
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Liang, Xiao-Dong
AU  - Liang XD
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Song, Jian-Nan
AU  - Song JN
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Hou, Li-Na
AU  - Hou LN
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Wu, Jian-Nan
AU  - Wu JN
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Guo, Ying
AU  - Guo Y
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Feng, Dan-Dan
AU  - Feng DD
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Sun, Yi
AU  - Sun Y
AD  - Department of Anesthesiology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 
      024000, P.R. China.
FAU - Yu, Jian-Bo
AU  - Yu JB
AD  - Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, 
      Tianjin Medical University, Tianjin 300102, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20230324
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC10133796
OTO - NOTNLM
OT  - PTEN-induced putative kinase 1
OT  - heme oxygenase-1
OT  - mitochondrial
OT  - pyroptosis
OT  - renal tubular epithelial cells
COIS- The authors declare that they have no competing interests.
EDAT- 2023/05/01 06:42
MHDA- 2023/05/01 06:43
PMCR- 2023/03/24
CRDT- 2023/05/01 03:28
PHST- 2022/09/13 00:00 [received]
PHST- 2023/02/24 00:00 [accepted]
PHST- 2023/05/01 06:43 [medline]
PHST- 2023/05/01 06:42 [pubmed]
PHST- 2023/05/01 03:28 [entrez]
PHST- 2023/03/24 00:00 [pmc-release]
AID - ETM-25-5-11912 [pii]
AID - 10.3892/etm.2023.11912 [doi]
PST - epublish
SO  - Exp Ther Med. 2023 Mar 24;25(5):213. doi: 10.3892/etm.2023.11912. eCollection 
      2023 May.