All-trans retinoic acid can regulate the expressions of gelatinases and apolipoprotein E in glomerulosclerosis rats

Abstract

Apolipoprotein E (apoE) is an important plasma protein in cholesterol homeostasis and plays a key role in the pathogenesis of glomerulosclerosis (GS). Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The abnormal expressions of gelatinases are implicated in the pathogenesis of extracellular matrix accumulation. All-trans retinoic acid (ATRA) is an import biological agent which can play a protective role against GS. We performed this investigation to explore whether ATRA could regulate the expressions of gelatinases and apoE in the glomerulus of GS rats. 120 Wistar rats were randomly divided into three groups: sham operation group (SHO), glomerulosclerosis model group without treatment (GS) and GS model group treated with ATRA (GA). The GS disease was established by uninephrectomy and adriamycin injection. At the end of 9 and 13weeks, the relevant samples were collected and determined. Compared with GS group at 9/13weeks, values of 24-hour urine total protein, 24-hour urine excretion for albumin, blood urea nitrogen, serum creatinine and glomerulosclerosis index, and protein expressions of apoE, transforming growth factor-βl (TGF-β1), α-smooth muscle actin, collagen-IV and fibronectin in glomerulus and mRNA expressions of apoE and TGF-β1 in renal tissue were significantly down-regulated by ATRA (each P<0.01). However, the expressions of MMP-2 and MMP-9 (mRNA, protein and activity) were enhanced in GA group than those in GS group. In conclusion, gelatinases are associated with apoE expression, and ATRA can increase the gelatinases expressions and reduce the accumulation of apoE in glomerulus of GS rats, but the detailed mechanism needs to be elucidated in the future.