PMID- 23457573
OWN - NLM
STAT- MEDLINE
DCOM- 20130828
LR  - 20220408
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 2
DP  - 2013
TI  - Cysteine-rich protein 61 plays a proinflammatory role in obstructive kidney 
      fibrosis.
PG  - e56481
LID - 10.1371/journal.pone.0056481 [doi]
LID - e56481
AB  - Cysteine-rich protein 61 (Cyr61) is a secreted matrix-associated protein that 
      regulates a broad spectrum of biological and cellular activities. This study 
      aimed to investigate the role of Cyr61 in progressive kidney fibrosis induced by 
      unilateral ureteral obstruction (UUO) surgery in mice. The expression of Cyr61 
      transcripts and proteins in the obstructed kidneys were increased from day 1 and 
      remained high until day 10 after surgery. Immunohistochemistry indicated that 
      Cyr61 was expressed mainly in renal tubular epithelial cells. The upregulated 
      Cyr61 in UUO kidneys was reduced in mice treated with pan-transforming growth 
      factor-beta (TGF-beta) antibody. The role of TGF-beta in tubular Cyr61 upregulation after 
      obstructive kidney injury was further supported by experiments showing that 
      TGF-beta1 stimulated Cyr61 expression in cultured tubular epithelial cells. Notably, 
      the upregulation of Cyr61 in UUO kidneys was followed by a marked increase in 
      monocyte chemoattractant protein 1 (MCP-1) transcripts and macrophage 
      infiltration, which were attenuated in mice treated with anti-Cyr61 antibodies. 
      This proinflammatory property of Cyr61 in inducing MCP-1 expression was further 
      confirmed in tubular epithelial cells cultured with Cyr61 protein. The anti-Cyr61 
      antibody in UUO mice also reduced the levels of collagen type 1-alpha1 transcripts, 
      collagen fibril accumulation evaluated by picrosirius red staining, and the 
      levels of alpha-smooth muscle actin (alpha-SMA) transcripts and proteins on day 4 after 
      surgery; however, the antifibrotic effect was not sustained. In conclusion, the 
      TGF-beta-mediated increase in tubular Cyr61 expression involved renal inflammatory 
      cell infiltration through MCP-1 induction during obstructive kidney injury. The 
      Cyr61 blockade attenuated kidney fibrosis in the early phase, but the 
      antifibrotic effect could not be sustained.
FAU - Lai, Chun-Fu
AU  - Lai CF
AD  - Department of Internal Medicine, National Taiwan University Hospital and College 
      of Medicine, Taipei, Taiwan.
FAU - Chen, Yung-Ming
AU  - Chen YM
FAU - Chiang, Wen-Chih
AU  - Chiang WC
FAU - Lin, Shuei-Liong
AU  - Lin SL
FAU - Kuo, Min-Liang
AU  - Kuo ML
FAU - Tsai, Tun-Jun
AU  - Tsai TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130215
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cysteine-Rich Protein 61)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Chemokine CCL2/genetics
MH  - Cysteine-Rich Protein 61/chemistry/genetics/immunology/*metabolism
MH  - Down-Regulation
MH  - Epithelial Cells/metabolism
MH  - Fibrosis
MH  - Inflammation/metabolism
MH  - Kidney/injuries/metabolism/*pathology
MH  - Kidney Tubules/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Molecular Sequence Data
MH  - Transforming Growth Factor beta/genetics
MH  - Up-Regulation
MH  - Ureteral Obstruction/complications
PMC - PMC3574066
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/03/05 06:00
MHDA- 2013/08/29 06:00
PMCR- 2013/02/15
CRDT- 2013/03/05 06:00
PHST- 2012/07/23 00:00 [received]
PHST- 2013/01/14 00:00 [accepted]
PHST- 2013/03/05 06:00 [entrez]
PHST- 2013/03/05 06:00 [pubmed]
PHST- 2013/08/29 06:00 [medline]
PHST- 2013/02/15 00:00 [pmc-release]
AID - PONE-D-12-22212 [pii]
AID - 10.1371/journal.pone.0056481 [doi]
PST - ppublish
SO  - PLoS One. 2013;8(2):e56481. doi: 10.1371/journal.pone.0056481. Epub 2013 Feb 15.