ANGIOTENSIN-III UP-REGULATES GENES INVOLVED IN KIDNEY DAMAGE IN MESANGIAL CELLS AND RENAL INTERSTITIAL FIBROBLASTS

Angiotensin (Ang) II is considered the effector peptide of the renin-a ngiotensin system (RAS) that acts as a renal growth factor. Some studi es have shown that the angiotensin degradation product Ang III present s some biological activities, though its role in renal pathology has n ot been explored. We have observed that in renal interstitial fibrobla sts Ang III induces c-fos gene expression, suggesting a potential role of Ang III in the control of cell proliferation. To study the involve ment of Ang III in matrix regulation, we determined whether Ang III in creased TGF-beta gene expression and fibronectin production in culture d rat mesangial cells and renal interstitial fibroblasts, the main eff ector cells in glomerular and interstitial fibrosis, respectively. In both cell types, treatment with Ang III (10(-7) M) for six hours up-re gulated gene expression of transforming growth factor-beta 1 (TGF-beta 1; 2.3- and 2.2-fold, respectively). This peptide also increased fibr onectin production in renal interstitial fibroblasts. All these data s uggest that Ang III could contribute to matrix accumulation. Activatio n of local RAS has been described during renal damage. Renal cells exp ress angiotensinogen mRNA that was up-regulated in response to Ang II and Ang III stimulation, and therefore both peptides may participate i n the generation of angiotensin peptides in the kidney. In conclusion, our results suggest that the angiotensin degradation product Ang III could participate in the pathogenesis of key events of renal diseases, supporting the hypothesis that other peptides of the RAS besides Ang II may be involved in renal injury.