PMID- 33238752
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220531
IS  - 1521-0499 (Electronic)
IS  - 0190-2148 (Linking)
VI  - 47
IP  - 2
DP  - 2021 Feb-Mar
TI  - BTB and CNC homology 1 inhibition ameliorates fibrosis and inflammation via 
      blocking ERK pathway in pulmonary fibrosis.
PG  - 67-77
LID - 10.1080/01902148.2020.1849448 [doi]
AB  - OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) are still suffering 
      from unfavorable survival. BTB and CNC homology1 (Bach1) is a regulator of 
      oxidative stress and participates in the pathogenesis of multiple lung diseases. 
      Thus, this study aimed to determine the effect of Bach1 knockdown on fibrosis and 
      inflammation in pulmonary fibrosis (PF) mice and cell models. METHODS: Bleomycin 
      induced PF mice were constructed and treated with Bach1 siRNA adenovirus 
      (BLM + Bach1 siRNA group), control siRNA adenovirus (BLM + Control siRNA group) 
      or normal saline (BLM group), then lung tissues were collected for Bach1 
      expression detection, H&E staining and Masson's trichrome staining. Afterwards, 
      collagen type I alpha 1 chain (COL1A1) and interleukin-6 (IL-6) expressions in 
      serum and bronchoalveolar lavage fluid (BALF) were examined. Subsequently, mouse 
      lung fibroblasts (MLFs) were collected from PF mice and treated with TGF-beta1 to 
      construct PF cell model, which was treated with Bach1 siRNA adenovirus 
      (TGF-beta1 + Bach1 siRNA group) and MAP kinase (ERK) inhibitor U0126 alone 
      (TGF-beta1 + U0126 group) or in combination (TGF-beta1 + U0126 + Bach1 siRNA group), 
      then alpha-smooth muscle actin (alpha-SMA), fibronectin 1 (Fn1), COL1A1, IL-6 
      expressions and cell viability were detected. RESULTS: Lung tissue Bach1 mRNA and 
      protein expressions were upregulated in PF mice compared to control mice. Bach1 
      knockdown reduced lung fibrosis (displayed by Masson's trichrome staining) and 
      inflammation (displayed by H&E staining), then downregulated serum and BALF 
      expressions of COL1A1 and IL-6 in PF mice. Subsequently, in PF cell model, Bach1 
      knockdown blocked ERK pathway, but did not affect Smads, c-Jun N-terminal kinase 
      (JNK) or thymoma viral proto-oncogene 1 (Akt) pathways. Further experiments 
      revealed that Bach1 knockdown repressed cell viability, alpha-SMA, Fn1, IL-6 and 
      COL1A1 expressions in PF cell model, then ERK inhibition by U0126 enhanced these 
      effects. CONCLUSIONS: Bach1 is involved in the PF pathogenesis via modulating ERK 
      signaling pathway.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Rheumatology, Liuzhou People's Hospital , Liuzhou , China.
FAU - Wang, Yongfu
AU  - Wang Y
AD  - Department of Rheumatology, First Affiliated Hospital of Baotou Medical College , 
      Baotou , China.
FAU - Lu, Fuai
AU  - Lu F
AD  - Department of Rheumatology, First Affiliated Hospital of Baotou Medical College , 
      Baotou , China.
FAU - Wang, Le
AU  - Wang L
AD  - Department of Rheumatology, Liuzhou People's Hospital , Liuzhou , China.
FAU - Miao, Liu
AU  - Miao L
AD  - Department of Cardiology, Liuzhou People's Hospital , Liuzhou , China.
FAU - Wang, Xiaoyuan
AU  - Wang X
AD  - Department of Intensive Care Unit, Liuzhou People's Hospital , Liuzhou , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201126
PL  - England
TA  - Exp Lung Res
JT  - Experimental lung research
JID - 8004944
RN  - 0 (Bach1 protein, mouse)
RN  - 0 (Basic-Leucine Zipper Transcription Factors)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 11056-06-7 (Bleomycin)
SB  - IM
MH  - Animals
MH  - Basic-Leucine Zipper Transcription Factors/*genetics
MH  - Bleomycin
MH  - Humans
MH  - *Idiopathic Pulmonary Fibrosis
MH  - Inflammation
MH  - Lung/metabolism
MH  - *MAP Kinase Signaling System
MH  - Mice
MH  - Transforming Growth Factor beta1/metabolism
OTO - NOTNLM
OT  - Bach1
OT  - ERK
OT  - fibrosis
OT  - inflammation
OT  - pulmonary fibrosis
EDAT- 2020/11/27 06:00
MHDA- 2022/01/14 06:00
CRDT- 2020/11/26 05:28
PHST- 2020/11/27 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2020/11/26 05:28 [entrez]
AID - 10.1080/01902148.2020.1849448 [doi]
PST - ppublish
SO  - Exp Lung Res. 2021 Feb-Mar;47(2):67-77. doi: 10.1080/01902148.2020.1849448. Epub 
      2020 Nov 26.