Effects of Retinoids on the TGF-β System and Extracellular Matrix in Experimental Glomerulonephritis

Abstract . Transforming growth factor—β1 (TGF-β1) overexpression plays a key role in the glomerular accumulation of extracellular matrix proteins in renal disease. Retinoids have previously been shown to significantly limit glomerular damage in rat experimental glomerulonephritis. Therefore, the effects of all-trans retinoic acid and isotretinoin on the components of the TGF-β system and extracellular matrix proteins in anti-Thy1.1-nephritis (Thy-GN) were investigated. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin ( n = 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8), i.e. , starting before or after induction of Thy-GN, respectively. Urinary TGF-β1 excretion was 60% lower in all-trans retinoic acid-treated animals with Thy-GN ( P P P P P P P