Suppressive effects of fish oil on mesangial cell proliferation in vitro and in vivo

Suppressive effects of fish oil on mesangial cell proliferation in vitro and in vivo. Mesangial cell proliferation is a characteristic feature of IgA nephropathy and many other forms of glomerulonephritis. Recent clinical studies have shown that dietary fish oil supplementation retards renal disease...

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Bibliographic Details
Published in:Kidney international 2000-03, Vol.57 (3), p.1027-1040
Main Authors: Grande, Joseph P., Walker, Henry J., Holub, Bruce J., Warner, Gina M., Keller, Dawn M., Haugen, James D., Donadio, James V., Dousa, Thomas P.
Format: Article
Language:English
Subjects:
Animals
antithymocyte serum
Biological and medical sciences
Cell Division - drug effects
Cells, Cultured
Cyclic AMP-Dependent Protein Kinases - metabolism
DHA
DNA - biosynthesis
Docosahexaenoic Acids - pharmacology
EPA
Fatty Acids - metabolism
Fatty Acids, Omega-3 - blood
Fatty Acids, Omega-3 - metabolism
Fish Oils - pharmacology
Glomerular Mesangium - cytology
Glomerular Mesangium - metabolism
Glomerulonephritis
Glomerulonephritis - immunology
Glomerulonephritis - pathology
Glomerulonephritis - urine
Immune Sera - immunology
Kidney - metabolism
Male
Medical sciences
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Phospholipids - metabolism
Platelet-Derived Growth Factor - pharmacology
proteinuria
Proteinuria - urine
Rats
Rats, Wistar
Thy 1.1
Thy-1 Antigens - immunology
Thymidine - antagonists & inhibitors
Thymidine - metabolism
ω3 polyunsaturated fatty acids
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Summary:Suppressive effects of fish oil on mesangial cell proliferation in vitro and in vivo. Mesangial cell proliferation is a characteristic feature of IgA nephropathy and many other forms of glomerulonephritis. Recent clinical studies have shown that dietary fish oil supplementation retards renal disease progression in patients with IgA nephropathy. The mechanism by which this effect occurs is unknown. The anti-Thy 1.1 (ATS) model of mesangial proliferative glomerulonephritis was employed to test the hypothesis that dietary fish oil supplementation reduces mesangial cell proliferation following acute injury. Subcultured rat mesangial cells were used to determine the in vitro effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the primary components of fish oil, on proliferation. Following antithymocyte serum (ATS) administration, proteinuria was significantly decreased in animals treated with fish oil compared with sesame oil-treated controls. In ATS rats given fish oil, there was less mesangial cell and matrix expansion, mesangiolysis, or basement membrane disruption (Δ% = -40%). ATS rats receiving fish oil had less glomerular cell proliferation (PCNA-Δ% = -50%) and a reduction of α-smooth muscle actin expression (Δ% = -27%) by mesangial cells. In subcultured rat mesangial cells, DHA, but not EPA, significantly inhibited proliferation. Fish oil inhibits mesangial cell activation and proliferation in ATS glomerulonephritis, reduces proteinuria, and decreases histologic evidence of glomerular damage. In vitro, the antiproliferative effects of fish oil are more likely related to the action of DHA. We suggest that orally administered fish oil, or purified DHA, may have a suppressive effect in acute phases or relapses of glomerulopathies by inhibiting activation and proliferation of mesangial cells.
ISSN:0085-2538
1523-1755
DOI:10.1046/j.1523-1755.2000.00930.x