Increased renal expression of monocyte chemoattractant protein-1 and osteopontin in ADPKD in rats

Kidney Int. 2001 Dec;60(6):2087-96. doi: 10.1046/j.1523-1755.2001.00065.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • Female
  • Heterozygote
  • Immunohistochemistry
  • In Situ Hybridization
  • Kidney / metabolism*
  • Kidney / pathology
  • Macrophages / pathology
  • Male
  • Osteopontin
  • Polycystic Kidney, Autosomal Dominant / metabolism*
  • Polycystic Kidney, Autosomal Dominant / pathology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Inbred Strains
  • Reference Values
  • Sex Characteristics
  • Sialoglycoproteins / genetics
  • Sialoglycoproteins / metabolism*


  • Chemokine CCL2
  • RNA, Messenger
  • SPP1 protein, human
  • Sialoglycoproteins
  • Spp1 protein, rat
  • Osteopontin