PMID- 23152296
OWN - NLM
STAT- MEDLINE
DCOM- 20130516
LR  - 20151119
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 304
IP  - 6
DP  - 2013 Mar 15
TI  - Pirfenidone inhibits macrophage infiltration in 5/6 nephrectomized rats.
PG  - F676-85
LID - 10.1152/ajprenal.00507.2012 [doi]
AB  - Tubulointerstitial macrophage infiltration is a hallmark of chronic kidney 
      disease involved in the progression of renal fibrosis. Pirfenidone is a newly 
      identified antifibrotic drug, the potential mechanism of which remains unclear. 
      The aim of this study was to investigate the effects of pirfenidone on M1/M2 
      macrophage infiltration in nephrectomized rats. Nephrectomized rats were treated 
      with pirfenidone by gavage for 12 wk. Twenty-four hour urinary protein, 
      N-acetyl-beta-D-glycosaminidase (NAG) activity, systolic blood pressure, and 
      C-reactive protein were determined. Paraffin-embedded sections were stained for 
      CD68, CCR7, and CD163 macrophages. Monocyte chemoattractant protein-1 (MCP-1) and 
      macrophage inflammatory protein-1alpha (MIP-1alpha), as well as M1 and M2 macrophages 
      secretory markers, were evaluated by real-time RT-PCR and Western blotting 
      analysis. Pirfenidone significantly improved the elevated proteinuria and NAG 
      activity from week 2 onward after surgery. Pirfenidone attenuated interstitial 
      fibrosis and decreased expression of fibrotic markers including transforming 
      growth factor-beta(1), connective tissue growth factor, alpha-smooth muscle actin, 
      fibronectin, and fibroblast-specific protein-1. Pirfenidone significantly 
      decreased the infiltrating macrophages. The number of M1 and M2 macrophages was 
      significantly lower after pirfenidone treatment. MCP-1 and MIP-1alpha were increased 
      in nephrectomized rats at mRNA and protein levels. Pirfenidone treatment 
      significantly inhibited their expression. The TNF-alpha, IL-6, and nitric oxide 
      synthases-2 expressed by M1 macrophages were increased in nephrectomized rats, 
      and pirfenidone significantly attenuated their expression. Pirfenidone treatment 
      also significantly decreased arginase-1, dectin-1, CD206, and CD86 expressed by 
      M2 macrophages. Thus pirfenidone inhibits M1 and M2 macrophage infiltration in 
      5/6 nephrectomized rats, which suggests its efficacy in the early and late 
      periods of renal fibrosis.
FAU - Chen, Jun-Feng
AU  - Chen JF
AD  - Institute of Nephrology, Zhong Da Hospital, Southeast University School of 
      Medicine, Nanjing, China.
FAU - Ni, Hai-Feng
AU  - Ni HF
FAU - Pan, Ming-Ming
AU  - Pan MM
FAU - Liu, Hong
AU  - Liu H
FAU - Xu, Min
AU  - Xu M
FAU - Zhang, Ming-Hui
AU  - Zhang MH
FAU - Liu, Bi-Cheng
AU  - Liu BC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121114
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Biomarkers)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL3)
RN  - 0 (Pyridones)
RN  - D7NLD2JX7U (pirfenidone)
RN  - EC 3.2.1.52 (Acetylglucosaminidase)
SB  - IM
MH  - Acetylglucosaminidase/metabolism
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology/*therapeutic use
MH  - Biomarkers/metabolism
MH  - Blood Pressure/drug effects
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CCL3/metabolism
MH  - Drug Evaluation, Preclinical
MH  - Kidney/drug effects/metabolism/pathology
MH  - Macrophages/*drug effects
MH  - Male
MH  - Nephrectomy
MH  - Nephrosclerosis/*drug therapy/immunology
MH  - Phenotype
MH  - Proteinuria/drug therapy
MH  - Pyridones/pharmacology/*therapeutic use
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Renal Insufficiency, Chronic/*drug therapy/enzymology/immunology/pathology
EDAT- 2012/11/16 06:00
MHDA- 2013/05/17 06:00
CRDT- 2012/11/16 06:00
PHST- 2012/11/16 06:00 [entrez]
PHST- 2012/11/16 06:00 [pubmed]
PHST- 2013/05/17 06:00 [medline]
AID - ajprenal.00507.2012 [pii]
AID - 10.1152/ajprenal.00507.2012 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2013 Mar 15;304(6):F676-85. doi: 
      10.1152/ajprenal.00507.2012. Epub 2012 Nov 14.