Angiotensin II Infusion Induces Nephrin Expression Changes and Podocyte Apoptosis

Abstract

Background/Aim: In in vitro studies, angiotensin (Ang) II has been demonstrated to promote podocyte apoptosis. The present study evaluates the effects of Ang II infusion in rats on podocyte nephrin expression and apoptosis and the molecular mechanisms involved in Ang II-induced proteinuria and mesangial expansion. Methods: Sprague-Dawley rats were randomly assigned to receive either normal saline or Ang II (400 ng·kg^–1·min^–1) by means of a mini-osmotic pump for variable time periods. Systolic blood pressure and urinary protein and albumin excretion rate measurements were carried out on days 7, 14, 21, and 28. The animals were sacrificed on days 14 and 28 and evaluated for serum creatinine, renal pathological changes, podocyte apoptosis, renal nephrin mRNA, and protein expression. Results: The Ang II-infused rats developed hypertension and proteinuria. On day 14, the Ang II-infused rats showed narrowing of the slit diaphragm, an increase in podocyte nephrin mRNA and protein expression, and alterations in its distribution along the foot processes. On day 28, the Ang II-infused rats demonstrated the presence of apoptotic podocytes and decreased nephrin mRNA and protein expression. There was a negative correlation between nephrin expression and the numbers of apoptotic podocytes (r = –0.63, p < 0.05). Conclusion: These results suggest that changes in nephrin expression may play a role in the pathogenesis of Ang II-induced podocyte apoptosis.

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

“…18 This suggests that Ang II may induce changes in nephrin expression and podocyte apoptosis in Ang II-infused rats. 19 Podocyte damage is likely an important factor contributing to the impairment of endothelial and mesangial cells and further proteinuria and glomerulosclerosis. 20 Based on these findings, we propose the following mechanisms of action for the effects of CTFG and podocalyxin in hypertensive rats: (1) under normal conditions, CTGF is present in podocytes and parietal epithelial cells but not in mesangial cells.…”

Angiotensin-(1–7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats

“…Thus, the absence of expression of nephrin in the mouse leads to severe podocyte abnormalities and massive proteinuria already in utero (44). Besides its ability to induce hypertension and proteinuria, ANG II decreases mRNA and protein expression of nephrin that plays a key role in the pathogenesis of ANG II-induced podocyte apoptosis (28,32). However, the mechanism for the induction of the expression of nephrin after infusion of ANG-(1-7) shown in our current study appears to have been proceeded independently of ANG II renal levels, as they remained unchanged after the 2-wk treatment with the heptapeptide.…”

HSP27/HSPB1 as an adaptive podocyte antiapoptotic protein activated by high glucose and angiotensin II

“…15 Ang II promoted apoptosis of the cultured rat and mouse podocytes. [18][19][20] However, Ang II-induced apoptosis in human podocytes is not well characterized.…”