PMID- 27959382
OWN - NLM
STAT- MEDLINE
DCOM- 20170313
LR  - 20181113
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Print)
IS  - 1107-3756 (Linking)
VI  - 39
IP  - 1
DP  - 2017 Jan
TI  - Bach1 siRNA attenuates bleomycin-induced pulmonary fibrosis by modulating 
      oxidative stress in mice.
PG  - 91-100
LID - 10.3892/ijmm.2016.2823 [doi]
AB  - Oxidative stress plays an essential role in inflammation and fibrosis. Bach1 is 
      an important transcriptional repressor that acts by modulating oxidative stress 
      and represents a potential target in the treatment of pulmonary fibrosis (PF). In 
      this study, we knocked down Bach1 using adenovirus-mediated small interfering 
      RNA (siRNA) to determine whether the use of Bach1 siRNA is an effective 
      therapeutic strategy in mice with bleomycin (BLM)‑induced PF. Mouse lung 
      fibroblasts (MLFs) were incubated with transforming growth 
      factor (TGF)-beta1 (5 ng/ml) and subsequently infected with recombined 
      adenovirus-like Bach1 siRNA1 and Bach1 siRNA2, while an empty adenovirus vector 
      was used as the negative control. The selected Bach1 siRNA with higher 
      interference efficiency was used for the animal experiments. A mouse model of 
      BLM-induced PF was established, and Bach1 siRNA (1x109 pfu) was administered to 
      the mice via the tail vein. The results revealed that the Bach1 mRNA and protein 
      levels were significantly downregulated by Bach1 siRNA. Furthermore, the MLFs 
      infected with Bach1 siRNA exhibited increased mRNA and protein expression levels 
      of heme oxygenase-1 and glutathione peroxidase 1, but decreased levels of TGF-beta1 
      and interleukin-6 in the cell supernatants compared with the cells exposed to 
      TGF-beta1 alone. Bach1 knockdown by siRNA also enhanced the expression of 
      antioxidant factors, but suppressed that of fibrosis‑related cytokines in mice 
      compared with the BLM group. Finally, the inflammatory infiltration of alveolar 
      and interstitial cells and the destruction of lung structure were significantly 
      attenuated in the mide administered Bach1 siRNA compared with those in the BLM 
      group. On the whole, our findings demonstrate that Bach1 siRNA exerts protective 
      effects against BLM-induced PF in mice. Our data may provide the basis for the 
      development of novel targeted therapeutic strategies for PF.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital 
      Medical University, Beijing 100069, P.R. China.
FAU - Zheng, Yi
AU  - Zheng Y
AD  - Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital 
      Medical University, Beijing 100069, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20161208
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Antioxidants)
RN  - 0 (Bach1 protein, mouse)
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (Cytokines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 11056-06-7 (Bleomycin)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Basic-Leucine Zipper Transcription Factors/genetics/*metabolism
MH  - Bleomycin
MH  - Bronchoalveolar Lavage Fluid
MH  - Cytokines/metabolism
MH  - Female
MH  - Fibroblasts/metabolism/pathology
MH  - Gene Knockdown Techniques
MH  - Lung/metabolism/pathology
MH  - Mice, Inbred C57BL
MH  - *Oxidative Stress
MH  - Pulmonary Fibrosis/*chemically induced/*genetics/pathology
MH  - RNA, Small Interfering/*metabolism
MH  - Reproducibility of Results
MH  - Transfection
MH  - Transforming Growth Factor beta1/metabolism
PMC - PMC5179191
EDAT- 2016/12/14 06:00
MHDA- 2017/03/14 06:00
PMCR- 2016/12/08
CRDT- 2016/12/14 06:00
PHST- 2015/12/31 00:00 [received]
PHST- 2016/12/02 00:00 [accepted]
PHST- 2016/12/14 06:00 [pubmed]
PHST- 2017/03/14 06:00 [medline]
PHST- 2016/12/14 06:00 [entrez]
PHST- 2016/12/08 00:00 [pmc-release]
AID - ijmm-39-01-0091 [pii]
AID - 10.3892/ijmm.2016.2823 [doi]
PST - ppublish
SO  - Int J Mol Med. 2017 Jan;39(1):91-100. doi: 10.3892/ijmm.2016.2823. Epub 2016 Dec 
      8.