J Physiol ; 1 : The aim of this study was to provide evidence for the antifibrotic potential of RAAS inhibitor RAASi treatment and to explore the exact mechanism of this protective effect.
We found that RAASi ameliorate diabetes-induced renal interstitial fibrosis and decrease profibrotic growth factor production. RAASi prevents fibrosis by acting directly on proximal tubular cells, and inhibits hyperglycaemia-induced growth factor production and thereby fibroblast activation.
CoMICs Episode 40: Hypertensive Nephropathy
These results suggest a novel therapeutic indication and potential of RAASi in the treatment of renal fibrosis. Hypertensive nephropathy kidney size vitro studies on proximal tubular cells and renal fibroblasts were also performed to further clarify the signal transduction pathways that are directly altered by hyperglycaemia.
After 5 weeks of diabetes, male Wistar rats were treated for two more weeks per os with the RAASi ramipril, losartan, spironolactone or eplerenone. HG increased growth factor production of HK-2 cells, which in turn induced activation and αSMA production of fibroblasts.
In proximal tubular cells, hyperglycaemia-induced growth factor production increased renal fibroblast transformation, contributing to the development of fibrosis. RAASi, even in non-antihypertensive doses, decreased the production of profibrotic factors and directly prevented fibroblast activation.
All these findings suggest a novel therapeutic role for RAASi in the treatment of renal fibrosis.