PMID- 21957176
OWN - NLM
STAT- MEDLINE
DCOM- 20120209
LR  - 20211020
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 302
IP  - 1
DP  - 2012 Jan 1
TI  - Mast cells are required for the development of renal fibrosis in the rodent 
      unilateral ureteral obstruction model.
PG  - F192-204
LID - 10.1152/ajprenal.00562.2010 [doi]
AB  - Mast cells are associated with inflammation and fibrosis. Whether they protect 
      against or contribute to renal fibrosis is unclear. Based on our previous 
      findings that mast cells can express and secrete active renin, and that 
      angiotensin (ANG II) is profibrotic, we hypothesized that mast cells play a 
      critical role in tubulointerstitial fibrosis. We tested this hypothesis in the 
      14-day unilateral ureteral obstruction (UUO) model in rats and mast 
      cell-deficient (MCD) mice (WBB6F1-W/Wv) and their congenic controls (CC). In the 
      14-day UUO rat kidney, mast cell number is increased and they express active 
      renin. Stabilizing mast cells in vivo with administration of cromolyn sodium 
      attenuated the development of tubulointerstitial fibrosis, which was confirmed by 
      measuring newly synthesized pepsin-soluble collagen and blind scoring of fixed 
      trichrome-stained kidney sections accompanied by spectral analysis. Fibrosis was 
      absent in UUO kidneys from MCD mice unlike that observed in the CC mice. Losartan 
      treatment reduced the fibrosis in the CC UUO kidneys. The effects of mast cell 
      degranulation and renin release were tested in the isolated, perfused kidney 
      preparation. Mast cell degranulation led to renin-dependent protracted flow 
      recovery. This demonstrates that mast cell renin is active in situ and the 
      ensuing ANG II can modulate intrarenal vascular resistance in the UUO kidney. 
      Collectively, the data demonstrate that mast cells are critical to the 
      development of renal fibrosis in the 14-day UUO kidney. Since renin is present in 
      human kidney mast cells, our work identifies potential targets in the treatment 
      of renal fibrosis.
FAU - Veerappan, Arul
AU  - Veerappan A
AD  - Dept. of Physiology and Biophysics, Weill Cornell Medical College, 1300 York 
      Ave., Box 75, New York, NY 10065, USA.
FAU - Reid, Alicia C
AU  - Reid AC
FAU - O'Connor, Nathan
AU  - O'Connor N
FAU - Mora, Rosalia
AU  - Mora R
FAU - Brazin, Jacqueline A
AU  - Brazin JA
FAU - Estephan, Racha
AU  - Estephan R
FAU - Kameue, Takashi
AU  - Kameue T
FAU - Chen, Jie
AU  - Chen J
FAU - Felsen, Diane
AU  - Felsen D
FAU - Seshan, Surya V
AU  - Seshan SV
FAU - Poppas, Dix P
AU  - Poppas DP
FAU - Maack, Thomas
AU  - Maack T
FAU - Silver, Randi B
AU  - Silver RB
LA  - eng
GR  - R01 DK060726/DK/NIDDK NIH HHS/United States
GR  - DK060726/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110928
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 11128-99-7 (Angiotensin II)
RN  - EC 3.4.23.15 (Renin)
RN  - JMS50MPO89 (Losartan)
SB  - IM
MH  - Angiotensin II/physiology
MH  - Animals
MH  - Cell Degranulation
MH  - Fibrosis
MH  - Humans
MH  - In Vitro Techniques
MH  - Kidney/metabolism/pathology
MH  - Kidney Diseases/drug therapy/*pathology
MH  - Losartan/therapeutic use
MH  - Male
MH  - Mast Cells/*physiology
MH  - Mice
MH  - Rats
MH  - Renin/*physiology
MH  - Renin-Angiotensin System/physiology
MH  - Ureteral Obstruction/*pathology
PMC - PMC3251335
EDAT- 2011/10/01 06:00
MHDA- 2012/02/10 06:00
PMCR- 2013/01/01
CRDT- 2011/09/30 06:00
PHST- 2011/09/30 06:00 [entrez]
PHST- 2011/10/01 06:00 [pubmed]
PHST- 2012/02/10 06:00 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - ajprenal.00562.2010 [pii]
AID - F-00562-2010 [pii]
AID - 10.1152/ajprenal.00562.2010 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2012 Jan 1;302(1):F192-204. doi: 
      10.1152/ajprenal.00562.2010. Epub 2011 Sep 28.