Proinflammatory gene expression and macrophage recruitment in the rat remnant kidney

Kidney Int. 2000 Oct;58(4):1664-76. doi: 10.1111/j.1523-1755.2000.00327.x.


Background: Macrophage (Mphi) infiltration may contribute to chronic renal injury. We therefore sought to examine the expression of genes associated with Mphi recruitment in the rat remnant kidney model.

Methods: Male Munich Wistar rats underwent 5/6 nephrectomy or sham operation (SHM, N = 18) and received no treatment (VEH, N = 18), enalapril 100 mg/L (ENA, N = 18), or candesartan 70 mg/L (CSN, N = 24) in drinking water. Competitive, quantitative reverse transcription-polymerase chain reaction was used to determine renal cortex mRNA levels for cell adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), the Mphi chemoattractant monocyte chemoattractant protein-1 (MCP-1), Mphi products interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), and the profibrotic cytokine transforming growth factor-beta1 (TGF-beta1), at intervals post-nephrectomy.

Results: Glomerular and interstitial Mphi infiltration in VEH rats was associated with an early (4 week) and sustained rise in MCP-1 and TGF-beta1 mRNA levels. Progressive increases in ICAM-1, VCAM-1, IL-1beta, and TNF-alpha expression followed at 8 and 12 weeks. Immunostaining in VEH rats localized TGF-beta1 to glomeruli, tubules, and interstitium; MCP-1 to tubules and interstitial cells; ICAM-1 to glomeruli; and IL-1beta and TNF-alpha to tubules and interstitial cells. At 12 weeks, both treatments normalized systolic blood pressure (ENA, 105 +/- 6; CSN, 97 +/- 3 mm Hg) and the urinary protein excretion rate (ENA, 8.4 +/- 0.9; CSN, 5.7 +/- 0.8 mg/day), prevented renal injury (focal and segmental glomerulosclerosis: ENA, 3.3 +/- 0.9; CSN, 1.3 +/- 0.4%), and suppressed Mphi infiltration and cytokine expression (with the exception of TNF-alpha) to near SHM levels.

Conclusions: These findings support the hypothesis that the coordinated up-regulation of several molecules regulating Mphi recruitment and activation is a fundamental response to renal mass ablation and is dependent on an intact renin-angiotensin system. We speculate that these responses may play a role in the pathogenesis of the ensuing glomerulosclerosis and tubulointerstitial fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / genetics
  • DNA Primers
  • Gene Expression / immunology
  • Glomerulosclerosis, Focal Segmental / immunology*
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-1 / genetics
  • Kidney / cytology
  • Kidney / immunology
  • Kidney / surgery
  • Macrophages / cytology*
  • Macrophages / immunology*
  • Male
  • Nephrectomy
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Renin-Angiotensin System / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta / genetics
  • Tumor Necrosis Factor-alpha / genetics
  • Vascular Cell Adhesion Molecule-1 / genetics


  • Chemokine CCL2
  • DNA Primers
  • Interleukin-1
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1