PMID- 30840292
OWN - NLM
STAT- MEDLINE
DCOM- 20200727
LR  - 20200727
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 4
DP  - 2019 Feb
TI  - Autophagy in pulmonary macrophages mediates lung inflammatory injury via c-Src 
      tyrosine kinase pathway activation during mechanical ventilation.
PG  - 1674-1680
LID - 17129 [pii]
LID - 10.26355/eurrev_201902_17129 [doi]
AB  - OBJECTIVE: It has been clearly demonstrated that autophagy plays a critical role 
      in mechanical ventilation-Induced lung injury (VILI). Herein, we first evaluated 
      the mutual effects of autophagy and c-Src signaling on the lung inflammatory 
      response to mechanical ventilation. MATERIALS AND METHODS: Mice were respectively 
      subjected to a lower or higher lung stretch induced by mechanical ventilation 
      with low (7 mL/kg) or high (28 mL/kg) tidal volume, before measuring the 
      activation of autophagy and c-Src signaling through LC3 lipidation and c-Src 
      phosphorylation, respectively. Bone marrow-derived macrophages (BMDMs) were 
      transfected with Atg5 siRNA and administered to AM-depleted mice to generate an 
      autophagy-deficient phenotype, and c-Src signaling was evaluated by Western blot 
      assay to determine the impact of autophagy on c-Src activation during VILI. 
      Afterwards, the c-Src pathway was then blocked using PP2, prior to the evaluation 
      of polymorphonuclear neutrophils (PMN), total cell counts in BAL fluid, and lung 
      injury scores, in order to elucidate the role of the c-Src pathway in 
      autophagy-mediated VILI. RESULTS: Both LC3-II and p-c-Src were remarkably 
      increased after mechanical ventilation, in a time-dependent and tidal 
      volume-dependent manner. Moreover, c-Src phosphorylation induced by ventilation 
      was significantly compromised in autophagy-deficient mice. On the other hand, 
      LC3-II expression did not change due to c-Src signaling abolishment. But the 
      inflammatory response induced by injurious ventilation was markedly attenuated by 
      PP2 or AM-abolishment, shown by PMN and total cell counts in BAL fluid, as well 
      as lung injury scores. CONCLUSIONS: Our results suggested that autophagy caused 
      VILI via regulating c-Src activation, which implies that c-Src may serve as a 
      promising therapeutic target in VILI.
FAU - Li, G
AU  - Li G
AD  - Department of Anesthesiology, People's Hospital of Rizhao, Jining Medical 
      University, Rizhao, China. 347754658@qq.com.
FAU - Li, Y
AU  - Li Y
FAU - Zheng, S-F
AU  - Zheng SF
FAU - Han, Y-B
AU  - Han YB
FAU - Bai, Q-L
AU  - Bai QL
FAU - Zhao, T
AU  - Zhao T
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - EC 2.7.10.2 (src-Family Kinases)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Inflammation/*metabolism/pathology
MH  - Lung/*metabolism/pathology
MH  - Macrophages, Alveolar/*metabolism/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ventilator-Induced Lung Injury/*metabolism/pathology
MH  - src-Family Kinases/*metabolism
EDAT- 2019/03/07 06:00
MHDA- 2020/07/28 06:00
CRDT- 2019/03/07 06:00
PHST- 2019/03/07 06:00 [entrez]
PHST- 2019/03/07 06:00 [pubmed]
PHST- 2020/07/28 06:00 [medline]
AID - 17129 [pii]
AID - 10.26355/eurrev_201902_17129 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1674-1680. doi: 
      10.26355/eurrev_201902_17129.