Amelioration of glomerulosclerosis with all-trans retinoic acid is linked to decreased plasminogen activator inhibitor-1 and α-smooth muscle actin

Abstract

Aim: To examine the effects of all-trans retinoic acid (atRA) on renal morphology and function as well as on renal plasminogen activator inhibitor-1 (PAI-1) expression and plasmin activity in rats with 5/6 nephrectomy. Methods: Adult male Sprague Dawley rats were given 5/6 nephrectomy or sham operation. Renal function was measured 2 weeks later. The nephrectomized rats were assigned to groups matched for proteinuria and treated with vehicle or atRA (5 or 10 mg/kg by gastric gavage once daily) for the next 12 weeks. Rats with sham operation were treated with vehicle. At the end of the treatments, kidneys were collected for histological examination, Western blot analysis, and enzymatic activity measurements. Results: The 5/6 nephrectomy promoted hypertension, renal dysfunction, and glomerulosclerosis. These changes were significantly reduced in the atRA-treated group. The expressions of PAI-1 and α-smooth muscle actin (α-SMA) were significantly increased in the vehicle-treated nephrectomized rats. Treatment with atRA significantly reduced the expressions of PAI-1 and α-SMA. However, plasmin activity remained unchanged following atRA treatment. Conclusion: Treatment with atRA ameliorates glomerulosclerosis and improves renal function in rats with 5/6 nephrectomy. This is associated with a decrease in PAI-1 and α-SMA, but not with a change in plasmin activity.

All-Trans Retinoic Acid Treatment Is Associated with Prohibitin Expression in Renal Interstitial Fibrosis Rats

“…Some investigations [14–16] reported that ATRA could play a protective role in some renal diseases, but the detailed mechanism was not clear. Interestingly, ATRA treatment can suppress the generation of ROS [12], and have an anti-oxidative effect [17].…”

The effect of connective tissue growth factor on renal fibrosis and podocyte injury in hypertensive rats

“…The interstitial space is very sparse and not detectable, and the expression of a-SMA is exclusively confined in the intrarenal arteries in WKY groups. 27 It is possible that tubular epithelial cells, mesangial cells, and interstitial cells can transform into myofibroblasts, and these changes reflect dedifferentiation of renal tissue during the injury/repair process (hypertensive). The present results showing enhanced expression of CTGF, a-SMA, and collagen-III in the kidney with glomerular sclerosis and interstitial fibrosis, predicts a disrupted interaction between podocytes and CTGF.…”

Association of all-trans retinoic acid treatment with the renin-angiotensin aldosterone system expression in glomerulosclerosis rats

“…These results are similar to those reported elsewhere. 15,16 Activation of the RAAS contributes to the pathogenesis and progression of renal diseases. ACE1, a key enzyme of the RAAS, can convert the inactive angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II.…”