PMID- 31228816
OWN - NLM
STAT- MEDLINE
DCOM- 20200217
LR  - 20200217
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 74
DP  - 2019 Sep
TI  - Inhibitory effects of pirfenidone on fibroblast to myofibroblast transition in 
      rheumatoid arthritis-associated interstitial lung disease via the downregulation 
      of activating transcription factor 3 (ATF3).
PG  - 105700
LID - S1567-5769(19)30230-9 [pii]
LID - 10.1016/j.intimp.2019.105700 [doi]
AB  - OBJECTIVE: Pirfenidone (PFD) is an oral anti-fibrotic drug used for idiopathic 
      pulmonary fibrosis (IPF) therapy. We determined the role of activating 
      transcription factor 3 (ATF3) and the effect of PFD on fibroblast to 
      myofibroblast transition (FMT) in rheumatoid arthritis-associated interstitial 
      lung disease (RA-ILD). METHODS: RA-ILD lung specimens were obtained by CT-guided 
      percutaneous transthoracic biopsy. A pulmonary fibrosis mouse model was 
      established by the intratracheal injection of bleomycin. Pathological variation 
      and the expression of alpha-SMA and ATF3 were observed by H&E, Masson and 
      immunofluorescence staining. Primary human lung fibroblasts (pHLFs) were isolated 
      from lung tissues that were pathologically confirmed to be normal by 
      pneumonectomy. Cell viability was detected using an MTT assay. Cell migration and 
      invasion were detected using a Transwell chamber. The protein levels of alpha-SMA, 
      ATF3, Smad3 and p-Smad3 were measured by Western blot. HLFs were infected with 
      lentiviruses expressing ATF3 or scrambled shRNA. RESULTS: ATF3 was dramatically 
      upregulated in lung tissues from both bleomycin-induced mice and patients with 
      RA-ILD compared with controls. The upregulation of ATF3 and the accumulation of 
      collagen in the lung tissues of mice with pulmonary fibrosis were reduced by PFD. 
      PFD significantly inhibited increases in the proliferation, invasion and 
      migration of pHLFs stimulated by TGF-beta1. Moreover, we observed the inhibitory 
      effect of PFD on FMT via the downregulation of ATF3, which was further confirmed 
      in ATF3 knockdown (KD) pHLFs. CONCLUSIONS: This work shows the inhibitory effect 
      of PFD on FMT in pHLFs, which is mediated by the downregulation of ATF3. Our 
      findings suggest that PFD might have therapeutic potential for the treatment of 
      RA-ILD.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Wu, Chaochen
AU  - Wu C
AD  - Department of Rheumatology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou, PR China.
FAU - Lin, Haobo
AU  - Lin H
AD  - Department of Rheumatology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou, PR China.
FAU - Zhang, Xiao
AU  - Zhang X
AD  - Department of Rheumatology, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou, PR China. Electronic address: 
      xiaozhangggh@126.com.
LA  - eng
PT  - Journal Article
DEP - 20190619
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (ATF3 protein, human)
RN  - 0 (Activating Transcription Factor 3)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Atf3 protein, mouse)
RN  - 0 (Pyridones)
RN  - D7NLD2JX7U (pirfenidone)
SB  - IM
MH  - Activating Transcription Factor 3/genetics/*metabolism
MH  - Adult
MH  - Aged
MH  - Animals
MH  - Anti-Inflammatory Agents/*therapeutic use
MH  - Arthritis, Rheumatoid/*drug therapy
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Female
MH  - Fibroblasts/*physiology
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Lung/*metabolism/pathology
MH  - Lung Diseases, Interstitial/*drug therapy
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Myofibroblasts/*physiology
MH  - Pulmonary Fibrosis/*drug therapy
MH  - Pyridones/*therapeutic use
OTO - NOTNLM
OT  - Activating transcription factor 3 (ATF3)
OT  - Interstitial lung disease
OT  - Pirfenidone
OT  - Rheumatoid arthritis
EDAT- 2019/06/23 06:00
MHDA- 2020/02/18 06:00
CRDT- 2019/06/23 06:00
PHST- 2019/01/31 00:00 [received]
PHST- 2019/06/01 00:00 [revised]
PHST- 2019/06/13 00:00 [accepted]
PHST- 2019/06/23 06:00 [pubmed]
PHST- 2020/02/18 06:00 [medline]
PHST- 2019/06/23 06:00 [entrez]
AID - S1567-5769(19)30230-9 [pii]
AID - 10.1016/j.intimp.2019.105700 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2019 Sep;74:105700. doi: 10.1016/j.intimp.2019.105700. Epub 
      2019 Jun 19.