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


METHODS
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.


RESULTS
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 (delta% = -40%). ATS rats receiving fish oil had less glomerular cell proliferation (PCNA-delta% = -50%) and a reduction of alpha-smooth muscle actin expression (delta% = -27%) by mesangial cells. In subcultured rat mesangial cells, DHA, but not EPA, significantly inhibited proliferation.


CONCLUSIONS
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.
Grande
J P
JP
Department of Internal Medicine, Mayo Foundation, Rochester, Minnesota, USA. grande.joseph@mayo.edu
Walker
H J
HJ
Holub
B J
BJ
Warner
G M
GM
Keller
D M
DM
Haugen
J D
JD
Donadio
J V
JV
Dousa
T P
TP
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000652:urine; D007106:Immune Sera / Q000276:immunology; D007668:Kidney / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens / Q000276:immunology; D013936:Thymidine / Q000037:antagonists & inhibitors / Q000378:metabolism
D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007106:Immune Sera; D010743:Phospholipids; D010982:Platelet-Derived Growth Factor; D018800:Thy-1 Antigens; D004281:Docosahexaenoic Acids; D004247:DNA; D017868:Cyclic AMP-Dependent Protein Kinases; D013936:Thymidine