PMID- 37418084
OWN - NLM
STAT- MEDLINE
DCOM- 20230829
LR  - 20230831
IS  - 1573-4978 (Electronic)
IS  - 0301-4851 (Linking)
VI  - 50
IP  - 9
DP  - 2023 Sep
TI  - GGA (geranylgeranylacetone) ameliorates bleomycin-induced lung inflammation and 
      pulmonary fibrosis by inhibiting apoptosis and oxidative stress.
PG  - 7215-7224
LID - 10.1007/s11033-023-08590-3 [doi]
AB  - BACKGROUND: Fibrosis is a response to ongoing cellular injury, disruption, and 
      tissue remodeling, the pathogenesis of which is unknown, and is characterized by 
      extracellular matrix deposition. The antifibrotic effect of Geranylgeranylacetone 
      (GGA), as an inducer of Heat shock protein 70 (HSP70), in liver, kidney and 
      pulmonary fibrosis has been supported by multiple preclinical evidence. However, 
      despite advances in our understanding, the precise roles of HSP70 in fibrosis 
      require further investigation. The purpose of this study was to investigate 
      whether GGA could participate in the progression of pulmonary fibrosis in mice 
      through apoptosis, oxidative stress and inflammation. METHODS AND RESULTS: B-cell 
      lymphoma-2(Bcl-2) and Bcl2-Associated X (Bax) are two proteins related to 
      apoptosis. Anti-apoptotic factor Bcl-2 and pro-apoptotic factor Bax are often 
      involved in the apoptotic process in the form of dimer. Immunofluorescence and 
      Western blot results showed that bleomycin (BLM) and transforming growth factor-beta 
      (TGF-beta) inhibited Bcl-2 expression and promoted Bax expression in vitro and in 
      vivo, respectively. In contrast, GGA treatment reverses this change. Reactive 
      oxygen species (ROS), Malondialdehyde (MDA) and superoxide dismutase (SOD) are 
      markers of oxidative stress, which often reflect oxidative injury of cells. The 
      detection of ROS, MDA and SOD expression showed that TGF-beta and BLM treatment 
      could significantly promote oxidative stress, while GGA treatment could alleviate 
      oxidative stress damage. In addition, BLM significantly elevated Tumor necrosis 
      factor-alpha(TNF-alpha), Interleukin1beta (IL-1beta) and Interleukin 6 (IL-6), while 
      scutellarin reversed the above alterations except for that of GGA. RESULTS: Taken 
      together, GGA suppressed apoptotic, oxidative stress and inflammation in 
      BLM-induced pulmonary fibrosis.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature B.V.
FAU - Zhou, Rong
AU  - Zhou R
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
FAU - Jin, Chaomei
AU  - Jin C
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
FAU - Jiao, Linlin
AU  - Jiao L
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
FAU - Zhang, Siyu
AU  - Zhang S
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
FAU - Tian, Mei
AU  - Tian M
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
FAU - Liu, Jiamin
AU  - Liu J
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
FAU - Yang, Songtai
AU  - Yang S
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China.
FAU - Yao, Wu
AU  - Yao W
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. 
      yaowu@zzu.edu.cn.
FAU - Zhou, Fang
AU  - Zhou F
AUID- ORCID: 0000-0002-8211-9181
AD  - Department of Occupational and Environmental Health Science, College of Public 
      Health, Zhengzhou University, Zhengzhou, Henan province, 450001, China. 
      zhoufang@zzu.edu.cn.
LA  - eng
GR  - 222300420537/the Natural Science Foundation of Henan Province/
PT  - Journal Article
DEP - 20230707
PL  - Netherlands
TA  - Mol Biol Rep
JT  - Molecular biology reports
JID - 0403234
RN  - S8S8451A4O (geranylgeranylacetone)
RN  - 0 (Reactive Oxygen Species)
RN  - 11056-06-7 (Bleomycin)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Pulmonary Fibrosis/chemically induced/drug therapy/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Bleomycin/pharmacology
MH  - bcl-2-Associated X Protein/metabolism
MH  - Oxidative Stress
MH  - Inflammation/chemically induced/drug therapy/metabolism
MH  - Fibrosis
MH  - *Pneumonia
MH  - Transforming Growth Factor beta/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Apoptosis
MH  - Superoxide Dismutase/metabolism
MH  - Lung/metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - BEAS-2B cell
OT  - Epithelial-mesenchymal transition (EMT)
OT  - Inflammation
OT  - Oxidative stress
OT  - Pulmonary fibrosis
EDAT- 2023/07/07 13:04
MHDA- 2023/08/29 12:42
CRDT- 2023/07/07 11:12
PHST- 2023/03/14 00:00 [received]
PHST- 2023/06/13 00:00 [accepted]
PHST- 2023/08/29 12:42 [medline]
PHST- 2023/07/07 13:04 [pubmed]
PHST- 2023/07/07 11:12 [entrez]
AID - 10.1007/s11033-023-08590-3 [pii]
AID - 10.1007/s11033-023-08590-3 [doi]
PST - ppublish
SO  - Mol Biol Rep. 2023 Sep;50(9):7215-7224. doi: 10.1007/s11033-023-08590-3. Epub 
      2023 Jul 7.