PMID- 37938537
OWN - NLM
STAT- Publisher
LR  - 20231108
IS  - 1559-0305 (Electronic)
IS  - 1073-6085 (Linking)
DP  - 2023 Nov 8
TI  - Hyperoxia can Induce Lung Injury by Upregulating AECII Autophagy and Apoptosis 
      Via the mTOR Pathway.
LID - 10.1007/s12033-023-00945-2 [doi]
AB  - Oxygen therapy is a crucial medical intervention, but it is undeniable that it 
      can lead to lung damage. The mTOR pathway plays a pivotal role in governing cell 
      survival, including autophagy and apoptosis, two phenomena deeply entwined with 
      the evolution of diseases. However, it is unclarified whether the mTOR pathway is 
      involved in hyperoxic acute lung injury (HALI). The current study aims to clarify 
      the molecular mechanism underlying the pathogenesis of HALI by constructing in 
      vitro and in vivo models using H(2)O(2) and hyperoxia exposure, respectively. To 
      investigate the role of mTOR, the experiment was divided into five groups, 
      including normal group, injury group, mTOR inhibitor group, mTOR activator group, 
      and DMSO control group. Western blotting, Autophagy double labeling, TUNEL 
      staining, and HE staining were applied to evaluate protein expression, autophagy 
      activity, cell apoptosis, and pathological changes in lung tissues. Our data 
      revealed that hyperoxia can induce autophagy and apoptosis in Type II alveolar 
      epithelial cell (AECII) isolated from the treated rats, as well as injuries in 
      the rat lung tissues; also, H(2)O(2) stimulation increased autophagy and 
      apoptosis in MLE-12 cells. Noticeably, the experiments performed in both in vitro 
      and in vivo models proved that the mTOR inhibitor Rapamycin (Rapa) functioned 
      synergistically with hyperoxia or H(2)O(2) to promote AECII autophagy, which led 
      to increased apoptosis and exacerbated lung injury. On the contrary, activation 
      of mTOR with MHY1485 suppressed autophagy activity, consequently resulting in 
      reduced apoptosis and lung injury in H(2)O(2)-challenged MLE-12 cells and 
      hyperoxia-exposed rats. In conclusion, hyperoxia caused lung injury via 
      mTOR-mediated AECII autophagy.
CI  - (c) 2023. The Author(s).
FAU - Ren, Yingcong
AU  - Ren Y
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Qin, Song
AU  - Qin S
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Liu, Xinxin
AU  - Liu X
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Feng, Banghai
AU  - Feng B
AD  - Department of Critical Care Medicine, Zunyi Hospital of Traditional Chinese 
      Medicine, Zunyi, 563000, Guizhou, China.
FAU - Liu, Junya
AU  - Liu J
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Zhang, Jing
AU  - Zhang J
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Yuan, Ping
AU  - Yuan P
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Yu, Kun
AU  - Yu K
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Mei, Hong
AU  - Mei H
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China.
FAU - Chen, Miao
AU  - Chen M
AUID- ORCID: 0009-0003-0170-0965
AD  - Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical 
      University, Zunyi, 563000, Guizhou, China. chenmiaoicu@163.com.
LA  - eng
GR  - No. 81960024/National Natural Science Foundation of China/
GR  - No. 81960362/National Natural Science Foundation of China/
GR  - No.2020-4Y199/the Science and Technology Department of Guizhou Province/
GR  - No: ZK- 2022- 660/the Science and Technology Department of Guizhou Province/
GR  - No: ZK- 2023- 554/the Science and Technology Department of Guizhou Province/
PT  - Journal Article
DEP - 20231108
PL  - Switzerland
TA  - Mol Biotechnol
JT  - Molecular biotechnology
JID - 9423533
SB  - IM
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Hyperoxic acute lung injury
OT  - Type II alveolar epithelial cells
OT  - mTOR
EDAT- 2023/11/08 12:44
MHDA- 2023/11/08 12:44
CRDT- 2023/11/08 11:30
PHST- 2023/06/27 00:00 [received]
PHST- 2023/10/11 00:00 [accepted]
PHST- 2023/11/08 12:44 [medline]
PHST- 2023/11/08 12:44 [pubmed]
PHST- 2023/11/08 11:30 [entrez]
AID - 10.1007/s12033-023-00945-2 [pii]
AID - 10.1007/s12033-023-00945-2 [doi]
PST - aheadofprint
SO  - Mol Biotechnol. 2023 Nov 8. doi: 10.1007/s12033-023-00945-2.