title: Nuclear (receptor) power: retinoids in rat mesangioproliferative disease.
abstract: Cytokine-driven proliferation and inflammation play important roles in the response of the kidney to injury and precede the development of glomerulosclerosis. There is great interest in agents which may interfere with such proliferation and inflammation. Therefore, a rat model of mesangioproliferative glomerulonephritis was studied and the effects of all-trans retinoid acid (RA) and isotretinoin, powerful anti-proliferative and anti-inflammatory substances, on glomerular damage and cell proliferation were examined. The use of retinoids was also warranted because of their known (suppressive) effects on genes involved in the pathogenesis of renal damage. RA prevented the blood pressure increase evoked by anti-Thy1.1 nephritis. Treatment with either RA or isotretinoin reduced the albumin excretion rate by 70%. Periodic acid-Schiff (PAS) stains revealed significantly fewer glomerular cells in nephritic rats treated with retinoids. Similarly, the number of mitoses and of cells which stained positively for proliferating cell nuclear antigen was significantly less in nephritic glomeruli treated with retinoids compared with the vehicle-treated group. Glomerular expression of platelet-derived growth factor B-chain was significantly reduced in the presence of retinoids. It was concluded that retinoids limit glomerular proliferation, glomerular lesions and albuminuria in an established model of renal damage. These findings point to retinoids as potential novel modulators of glomerular injury.
authors.affiliation: Department of Nephrology, University Hospital, Bergheimerstrasse 56a, D-69115 Heidelberg, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Wagner
mesh_terms: D000818:Animals; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism* / Q000627:therapeutic use*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D012176:Retinoids