PMID- 16014038
OWN - NLM
STAT- MEDLINE
DCOM- 20051013
LR  - 20220408
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 68
IP  - 2
DP  - 2005 Aug
TI  - MCP-1 is up-regulated in unstressed and stressed HO-1 knockout mice: 
      Pathophysiologic correlates.
PG  - 611-22
AB  - BACKGROUND: Up-regulation of heme oxygenase-1 (HO-1) occurs in, and often confers 
      protection to, the injured kidney. Up-regulation of monocyte chemoattractant 
      protein-1 (MCP-1) promotes not only acute and chronic nephritides but also acute 
      ischemic and nephrotoxic injury. The present study was stimulated by the 
      hypothesis that expression of MCP-1 is suppressed by HO-1, and analyzed the 
      effect of HO-1 on the expression of MCP-1 in stressed and unstressed conditions. 
      METHODS: Expression of MCP-1 and pathophysiologic correlates were examined in 
      HO-1 knockout (HO-1-/-) and wild-type (HO-1+/+) mice in the unstressed state in 
      young and aged mice, and following nephrotoxic and ischemic insults. RESULTS: In 
      unstressed HO-1-/- mice, plasma levels of MCP-1 protein were elevated, and MCP-1 
      mRNA expression was increased in circulating leukocytes and in the kidney. Such 
      early and heightened up-regulation of MCP-1 was eventually accompanied by 
      phenotypic changes in the aged kidney consistent with MCP-1, namely, 
      proliferative changes in glomeruli, tubulointerstitial disease, and up-regulation 
      of transforming growth factor-beta1 (TGF-beta1) and collagens I, III, and IV. In 
      response to a nephrotoxic insult such as hemoglobin, MCP-1 mRNA was up-regulated 
      in a markedly sustained manner in HO-1-/- mice. In response to a duration of 
      ischemia that exerted little effect in HO-1+/+ mice, HO-1-/- mice exhibited 
      higher expression of MCP-1 mRNA, enhanced activation of nuclear factor-kappaB 
      (NF-kappaB) (the transcription factor that regulates MCP-1), markedly greater 
      functional and structural renal injury, increased caspase-3 expression, and 
      increased mortality. CONCLUSION: In the absence of HO-1, expression of MCP-1 is 
      significantly and consistently enhanced in unstressed and stressed conditions. We 
      speculate that the protective effects of HO-1 in injured tissue may involve, at 
      least in part, the capacity of HO-1 to restrain up-regulation of MCP-1.
FAU - Pittock, Siobhan T
AU  - Pittock ST
AD  - Department of Pediatric and Adolescent Medicine, Division of Nephrology and 
      Hypertension, Mayo Clinic, Rochester, Minnesota 55905, USA.
FAU - Norby, Suzanne M
AU  - Norby SM
FAU - Grande, Joseph P
AU  - Grande JP
FAU - Croatt, Anthony J
AU  - Croatt AJ
FAU - Bren, Gary D
AU  - Bren GD
FAU - Badley, Andrew D
AU  - Badley AD
FAU - Caplice, Noel M
AU  - Caplice NM
FAU - Griffin, Matthew D
AU  - Griffin MD
FAU - Nath, Karl A
AU  - Nath KA
LA  - eng
GR  - DK068545/DK/NIDDK NIH HHS/United States
GR  - DK47060/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hemoglobins)
RN  - 0 (Membrane Proteins)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
SB  - IM
CIN - Kidney Int. 2005 Aug;68(2):896-7. PMID: 16014072
MH  - Age Factors
MH  - Animals
MH  - Chemokine CCL2/*genetics
MH  - Heme Oxygenase (Decyclizing)/*genetics
MH  - Heme Oxygenase-1
MH  - Hemoglobins/toxicity
MH  - Ischemia/mortality/pathology/*physiopathology
MH  - Kidney Diseases/mortality/pathology/*physiopathology
MH  - Kidney Glomerulus/pathology/physiopathology
MH  - Membrane Proteins
MH  - Mice
MH  - Mice, Knockout
MH  - Stress, Physiological/mortality/pathology/*physiopathology
MH  - Survival Rate
MH  - Up-Regulation
EDAT- 2005/07/15 09:00
MHDA- 2005/10/14 09:00
CRDT- 2005/07/15 09:00
PHST- 2005/07/15 09:00 [pubmed]
PHST- 2005/10/14 09:00 [medline]
PHST- 2005/07/15 09:00 [entrez]
AID - S0085-2538(15)50881-8 [pii]
AID - 10.1111/j.1523-1755.2005.00439.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Aug;68(2):611-22. doi: 10.1111/j.1523-1755.2005.00439.x.