PMID- 11737583
OWN - NLM
STAT- MEDLINE
DCOM- 20020129
LR  - 20061115
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 60
IP  - 6
DP  - 2001 Dec
TI  - Increased renal expression of monocyte chemoattractant protein-1 and osteopontin 
      in ADPKD in rats.
PG  - 2087-96
AB  - BACKGROUND: Human autosomal-dominant polycystic kidney disease (ADPKD) is 
      variable in the rate of deterioration of renal function, with end-stage renal 
      disease (ESRD) occurring in only approximately 50% of affected individuals. 
      Evidence suggests that interstitial inflammation may be important in the 
      development of ESRD in ADPKD. Han:SPRD rats manifest ADPKD that resembles the 
      human disease. Homozygous cystic (Cy/Cy) rats develop rapidly progressive PKD and 
      die near age 3 weeks. Heterozygous (Cy/+) females develop slowly progressive PKD 
      without evidence of renal dysfunction until the second year of life, whereas 
      heterozygous (Cy/+) males develop more aggressive PKD with renal failure 
      beginning by 8 to 12 weeks of age. METHODS: To examine the relationship between 
      proinflammatory chemoattractants and the development of interstitial inflammation 
      and ultimately renal failure in ADPKD, we evaluated monocyte chemoattractant 
      protein-1 (MCP-1) and osteopontin mRNAs and proteins in kidneys from Han:SRPD 
      rats. RESULTS: MCP-1 and osteopontin mRNAs, expressed at low levels in kidneys 
      from normal (+/+) animals at all ages, were markedly elevated in kidneys from 
      3-week-old Cy/Cy animals. In kidneys from heterozygous (Cy/+) adults of either 
      gender, MCP-1 and osteopontin mRNAs were more abundant than normal; MCP-1 mRNA 
      was more abundant in Cy/+ males than in females. Thus, chemoattractant mRNA 
      expression correlated with the development of renal failure in Cy/Cy and Cy/+ 
      rats. Osteopontin mRNA, localized by in situ hybridization, was moderately 
      expressed in the renal medulla of normal animals; however, this mRNA was 
      expressed at very high levels in the cystic epithelia of Cy/+ and Cy/Cy animals. 
      MCP-1 and osteopontin proteins, localized by immunohistochemistry, were weakly 
      detected in +/+ kidneys but were densely expressed in Cy/Cy and in adult Cy/+ 
      kidneys, primarily over cystic epithelium. Increased expression of 
      chemoattractants was associated with the accumulation of ED-1 positive cells 
      (macrophages) in the interstitium of cystic kidneys. CONCLUSIONS: We suggest that 
      proinflammatory chemoattractants have a role in the development of interstitial 
      inflammation and renal failure in ADPKD.
FAU - Cowley, B D Jr
AU  - Cowley BD Jr
AD  - Division of Nephrology & Hypertension, Department of Medicine, Hershey Medical 
      Center, Pennsylvania State University, Hershey, Pennsylvania, USA. 
      Ben-Cowley@ouhsc.edu
FAU - Ricardo, S D
AU  - Ricardo SD
FAU - Nagao, S
AU  - Nagao S
FAU - Diamond, J R
AU  - Diamond JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (SPP1 protein, human)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Spp1 protein, rat)
RN  - 106441-73-0 (Osteopontin)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Female
MH  - Heterozygote
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Kidney/*metabolism/pathology
MH  - Macrophages/pathology
MH  - Male
MH  - Osteopontin
MH  - Polycystic Kidney, Autosomal Dominant/*metabolism/pathology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Reference Values
MH  - Sex Characteristics
MH  - Sialoglycoproteins/genetics/*metabolism
EDAT- 2001/12/12 10:00
MHDA- 2002/01/30 10:01
CRDT- 2001/12/12 10:00
PHST- 2001/12/12 10:00 [pubmed]
PHST- 2002/01/30 10:01 [medline]
PHST- 2001/12/12 10:00 [entrez]
AID - S0085-2538(15)48102-5 [pii]
AID - 10.1046/j.1523-1755.2001.00065.x [doi]
PST - ppublish
SO  - Kidney Int. 2001 Dec;60(6):2087-96. doi: 10.1046/j.1523-1755.2001.00065.x.