PMID- 32587469
OWN - NLM
STAT- MEDLINE
DCOM- 20210607
LR  - 20210607
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2020
DP  - 2020
TI  - Pirfenidone Inhibits Hypoxic Pulmonary Hypertension through the NADPH/ROS/p38 
      Pathway in Adventitial Fibroblasts in the Pulmonary Artery.
PG  - 2604967
LID - 10.1155/2020/2604967 [doi]
LID - 2604967
AB  - Hypoxic pulmonary hypertension (HPH) is a devastating disease characterized by 
      progressive vasoconstriction and vascular remodeling. Pirfenidone (PFD) inhibits 
      the progression of HPH, though the molecular mechanisms remain unknown. This 
      study is aimed at determining the role and mechanism of PFD in HPH in human 
      pulmonary artery adventitial fibroblasts (HPAAFs), which were cultured under 
      normal or hypoxic conditions. NOX4 and Rac1 were inhibited or overexpressed by 
      shRNA or pcDNA3.1, respectively. Proliferation of HPAAFs was quantified by 
      colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assays to 
      assess cellular metabolic activity, cell counts, and ethynyldeoxyuridine (EdU) 
      assays to detect DNA synthesis. Migration of HPAAFs was assessed by a wound 
      healing assay. The expression levels of smooth muscle alpha-actin (a-SMA) and 
      procollagen I (COL1A1) were assessed by RT-PCR and western blot analysis. PFD 
      suppressed hypoxia-induced proliferation and migration of HPAAFs. Compared with 
      the hypoxic control group, PFD reduced the expression of a-SMA and procollagen I 
      (COL1A1). PFD reduced hypoxia-induced phosphorylation of p38 through the 
      NOX4/reactive oxygen species (ROS) signaling pathway. Moreover, Rac1 also 
      decreased hypoxia-induced phosphorylation of p38, without any cross-interaction 
      with NOX4. These findings demonstrate that PFD is a novel therapeutic agent to 
      prevent cell proliferation, migration, and fibrosis, which might be useful in 
      inhibiting vascular remodeling in patients with HPH.
CI  - Copyright (c) 2020 Song Zhang et al.
FAU - Zhang, Song
AU  - Zhang S
AD  - Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital 
      Affiliated to Shandong First Medical University, Jinan, China.
FAU - Yin, ZongXiu
AU  - Yin Z
AD  - Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital, 
      Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 
      China.
AD  - Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital 
      Affiliated to Shandong University, Jinan, China.
FAU - Qin, WeiDong
AU  - Qin W
AD  - Department of Critical Care Medicine, Qilu Hospital, Shandong University, Jinan, 
      China.
FAU - Ma, XiaoLi
AU  - Ma X
AUID- ORCID: 0000-0003-0279-8354
AD  - Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, 
      Jinan, China.
FAU - Zhang, Yao
AU  - Zhang Y
AD  - Central Laboratory, Jinan Central Hospital Affiliated to Shandong University, 
      Jinan, China.
FAU - Liu, EnXiu
AU  - Liu E
AD  - Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital, 
      Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 
      China.
AD  - Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital 
      Affiliated to Shandong University, Jinan, China.
FAU - Chu, YanBiao
AU  - Chu Y
AUID- ORCID: 0000-0003-1918-7031
AD  - Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital, 
      Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 
      China.
AD  - Department of Pulmonary and Critical Care Medicine, Jinan Central Hospital 
      Affiliated to Shandong University, Jinan, China.
LA  - eng
PT  - Journal Article
DEP - 20200611
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Pyridones)
RN  - 0 (Reactive Oxygen Species)
RN  - 53-59-8 (NADP)
RN  - D7NLD2JX7U (pirfenidone)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Movement/drug effects/genetics
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/*metabolism
MH  - NADP/*metabolism
MH  - Phosphorylation
MH  - Pulmonary Artery/*drug effects/*metabolism
MH  - Pyridones/*therapeutic use
MH  - Reactive Oxygen Species/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC7305537
COIS- None of the authors has a financial relationship with a commercial entity that 
      has an interest in the subject of this manuscript.
EDAT- 2020/06/27 06:00
MHDA- 2021/06/08 06:00
PMCR- 2020/06/11
CRDT- 2020/06/27 06:00
PHST- 2020/04/12 00:00 [received]
PHST- 2020/05/22 00:00 [accepted]
PHST- 2020/06/27 06:00 [entrez]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2021/06/08 06:00 [medline]
PHST- 2020/06/11 00:00 [pmc-release]
AID - 10.1155/2020/2604967 [doi]
PST - epublish
SO  - Mediators Inflamm. 2020 Jun 11;2020:2604967. doi: 10.1155/2020/2604967. 
      eCollection 2020.