PMID- 28933986
OWN - NLM
STAT- MEDLINE
DCOM- 20180427
LR  - 20181202
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Linking)
VI  - 33
IP  - 9
DP  - 2017 Nov
TI  - The Antiangiogenesis Effect of Pirfenidone in Wound Healing In Vitro.
PG  - 693-703
LID - 10.1089/jop.2017.0007 [doi]
AB  - Abstracts Purpose: Pirfenidone is mostly used in antifibrotic and 
      anti-inflammatory therapies. We have previously demonstrated that pirfenidone had 
      antifibrotic and anti-inflammatory effects on the wound healing process after 
      glaucoma filtration surgery in vitro and in vivo. Since the wound healing and 
      reactive scarring process simultaneously involves inflammation, fibrosis, and 
      angiogenesis, and angiogenesis plays a more important role in chronic or 
      prolonged wound healing, we tried to explore the antiangiogenesis effect in 
      pirfenidone and its potential multitarget function in regulating excessive 
      scarring. The aim of the present study was to investigate the antiangiogenesis 
      effect of pirfenidone. METHODS: The proliferation of human umbilical vein 
      endothelial cells (HUVECs) and human Tenon's fibroblasts (HTFs) were detected by 
      WST-1 assay. The cell viability of HUVECs was measured by Trypan Blue together 
      with lactate dehydrogenase, Annexin 5 experiment, and Ki-67 immunofluorescence 
      assay. The functions of HUVECs and HTFs were demonstrated using cell migration 
      assay, transwell invasion assay, and tube formation assay. The expression levels 
      of vascular endothelial growth factor-A (VEGF-A), VEGF receptor-2 (VEGFR-2), 
      neuropilin-1(NRP-1), and their downstream signaling proteins p-PI3K, PI3K, p-AKT, 
      AKT, p-mTOR, and mechanistic target of rapamycin (mTOR) were indicated by western 
      blot assay. The secretion of VEGF-A was detected by enzyme-linked immunosorbent 
      assay. RESULTS: Pirfenidone inhibited proliferation, migration, invasion, and 
      tube formation of HUVECs in vitro, and had an equivalent antiangiogenesis effect 
      when compared with Ranibizumab in HUVECs and HTFs. Pirfenidone downregulated 
      VEGF-A/VEGFR-2, VEGF-A/NRP-1, and its downstream signaling pathway protein 
      expression. CONCLUSIONS: Pirfenidone has an antiangiogenesis effect in the wound 
      healing process and may become an ideal multitarget antiscarring agent after 
      glaucoma filtration surgery.
FAU - Liu, Xiao'an
AU  - Liu X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Yang, Yangfan
AU  - Yang Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Guo, Xiujuan
AU  - Guo X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Liu, Liling
AU  - Liu L
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Wu, Kaili
AU  - Wu K
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
FAU - Yu, Minbin
AU  - Yu M
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University , Guangzhou, People's Republic of China .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170921
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Annexin A5)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Neurophysins)
RN  - 0 (Pyridones)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - D7NLD2JX7U (pirfenidone)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.10.1 (KDR protein, human)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Annexin A5/metabolism
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Blotting, Western
MH  - Cell Movement/physiology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/drug effects
MH  - Flow Cytometry
MH  - Human Umbilical Vein Endothelial Cells/drug effects
MH  - Humans
MH  - Ki-67 Antigen/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Neurophysins/metabolism
MH  - Pyridones/*pharmacology
MH  - Tenon Capsule/cytology
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Vascular Endothelial Growth Factor Receptor-2/metabolism
MH  - Wound Healing/*drug effects
OTO - NOTNLM
OT  - AKT signaling pathway
OT  - antiangiogenesis
OT  - antiscarring
OT  - multitarget
OT  - pirfenidone
OT  - wound healing process
EDAT- 2017/09/22 06:00
MHDA- 2018/04/28 06:00
CRDT- 2017/09/22 06:00
PHST- 2017/09/22 06:00 [pubmed]
PHST- 2018/04/28 06:00 [medline]
PHST- 2017/09/22 06:00 [entrez]
AID - 10.1089/jop.2017.0007 [pii]
AID - 10.1089/jop.2017.0007 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2017 Nov;33(9):693-703. doi: 10.1089/jop.2017.0007. Epub 
      2017 Sep 21.