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 stu dies 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 glomerulon ephritis was employed to test the hypothesis that dietary fish oil suppleme ntation reduces mesangial cell proliferation following acute injury. Subcul tured rat mesangial cells were used to determine the in vitro effects of ei cosapentaenoic acid (EPA) and docosahexaenoic acid (PHA), the primary compo nents of fish oil, on proliferation. Results. Following antithymocyte serum (ATS) administration, proteinuria wa s significantly decreased in animals treated with fish oil compared with se same oil-treated controls. In ATS rats given fish oil, there was Less mesan gial cell and matrix expansion, mesangiolysis, or basement membrane disrupt ion (Delta% = -40%). ATS rats receiving fish oil had less glomerular cell p roliferation (PCNA-Delta% = -50%) and a reduction of cr-smooth muscle actin expression (Delta% = -27%) by mesangial cells. Tn subcultured rat mesangia l 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 ev idence of glomerular damage. In vitro, the antiproliferative effects of fis h 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 ac ute phases or relapses of glomerulopathies by inhibiting activation and pro liferation of mesangial cells.