PMID- 33836346
OWN - NLM
STAT- MEDLINE
DCOM- 20210720
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 556
DP  - 2021 Jun 4
TI  - Effects of rapamycin and OSI-027 on alpha-SMA in lung tissue of SD rat pups with 
      hyperoxic lung injury.
PG  - 39-44
LID - S0006-291X(21)00272-2 [pii]
LID - 10.1016/j.bbrc.2021.02.061 [doi]
AB  - OBJECTIVE: To investigate the effect and significance of mammalian target of 
      rapamycin (mTOR) inhibitors on the expression of alpha-SMA in lung injury induced by 
      high volume fraction of inspired oxygen (hyperoxygen) in SD rat pups. METHODS: 
      Seventy-two Sprague-Dawley rat pups (age: 3 weeks) were randomly divided into 
      air + saline, hyperoxia + saline, hyperoxia + OSI-027, and hyperoxia + rapamycin 
      groups. Animal models were constructed (n = 18). Hyperoxia was induced by 
      continuous administration of 90% oxygen. Normal saline, OSI-027, and rapamycin 
      are administered by intraperitoneal injection on 1d, 3d, 6d, 8d, 10d, 13d of the 
      observation period, respectively. Following assessments were made on the 3rd, 
      7th, and 14th day of modeling: pathological changes in lung tissues, lung injury 
      score, Western Blot to assess the distribution and expressions of mTOR, pS6K1, 
      and alpha-SMA protein in lung tissues. RESULTS: In terms of time factors, the protein 
      expressions of mTOR, pS6K1, and alpha-SMA increased with time. Except for the air 
      group, the lung injury scores of the other groups increased with time, In terms 
      of grouping factors, lung injury score in the air group was significantly lower 
      than that in the other groups. In the hyperoxia group, the protein expressions of 
      mTOR, PS6K1, and alpha-SMA were significantly higher than those in the other groups. 
      The lung injury score in the hyperoxia group was significantly higher than that 
      in the other groups. The lung injury score in the hyperoxia OSI group was 
      significantly lower than that in the hyperoxia rapamycin group. CONCLUSION: In 
      hyperoxia lung injury, inhibiting the activation of mTOR signaling pathway can 
      effectively reduce the expression of alpha-SMA; however, only mTORC1/2 dual inhibitor 
      OSI-027 exhibited an anti-proliferative effect, and alleviated hyperoxia-induced 
      lung injury and fibrosis in SD rat pups.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Liang, Mulin
AU  - Liang M
AD  - Department of Neonatal Intensive Care Unit, The Fifth Affiliated Hospital, 
      Southern Medical University Guangzhou, China.
FAU - Dang, Hongxing
AU  - Dang H
AD  - Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing 
      Medical University, Chongqing, China.
FAU - Li, Qinghe
AU  - Li Q
AD  - Department of Neonatal Intensive Care Unit, The Fifth Affiliated Hospital, 
      Southern Medical University Guangzhou, China.
FAU - Huang, Weiben
AU  - Huang W
AD  - Department of Neonatal Intensive Care Unit, The Fifth Affiliated Hospital, 
      Southern Medical University Guangzhou, China.
FAU - Liu, Chengjun
AU  - Liu C
AD  - Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing 
      Medical University, Chongqing, China. Electronic address: liucwd@163.com.
LA  - eng
PT  - Journal Article
DEP - 20210406
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Acta2 protein, rat)
RN  - 0 (Actins)
RN  - 0 (Imidazoles)
RN  - 0 (OSI 027)
RN  - 0 (Triazines)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (Rps6kb1 protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Actins/*metabolism
MH  - Animals
MH  - Female
MH  - Fibrosis/drug therapy/metabolism/pathology
MH  - Hyperoxia/*metabolism/pathology
MH  - Imidazoles/*pharmacology/therapeutic use
MH  - Lung/*drug effects/*metabolism/pathology
MH  - Lung Injury/drug therapy/*metabolism/pathology
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/antagonists & inhibitors/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Triazines/*pharmacology/therapeutic use
OTO - NOTNLM
OT  - Anti-proliferative
OT  - Fibrosis
OT  - Signaling pathway
OT  - mTOR inhibitor
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2021/04/10 06:00
MHDA- 2021/07/21 06:00
CRDT- 2021/04/09 20:13
PHST- 2021/02/03 00:00 [received]
PHST- 2021/02/15 00:00 [accepted]
PHST- 2021/04/10 06:00 [pubmed]
PHST- 2021/07/21 06:00 [medline]
PHST- 2021/04/09 20:13 [entrez]
AID - S0006-291X(21)00272-2 [pii]
AID - 10.1016/j.bbrc.2021.02.061 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2021 Jun 4;556:39-44. doi: 
      10.1016/j.bbrc.2021.02.061. Epub 2021 Apr 6.