Hydrogen sulfide treatment attenuates Ang‐II induced endothelial‐mesenchymal transition in renal fibrosis in aged mice (857.2)

Advanced age and hypertension are risk factors for chronic kidney disease. Emerging evidence suggests endothelial‐mesenchymal transition (EndoMT) as a possible source of renal myofibroblasts which play a crucial role in renovascular fibrosis. This complex process is driven by transforming growth factor‐β (TGF‐β) and involves loss of endothelial cell polarity and acquisition of myofibroblast phenotype. Although angiotensin‐II (Ang‐II) activates TGF‐β expression in the kidney, it is not known whether exogenous ang‐II induces endoMT in aged mice. Hydrogen sulfide (H 2 S), a gasotransmitter has recently been shown to suppress phenotypic transformation in atrial and lung fibroblasts. In the present study, we hypothesized that Ang‐II induced endoMT contributes to renal fibrosis and treatment with H 2 S attenuates endoMT by inhibition of TGF‐β. Wild type mice were infused with Ang‐II (1000ng/Kg/min) using osmotic pumps for 4 weeks and treated without or with H 2 S in drinking water (30μM/L). Ang‐II treated animals showed significant renal injury on histology, increased expression of TGF‐β and double labeling of endothelial (CD31) and mesenchymal markers, fibroblast specific protein‐1(FSP‐1) and α‐smooth muscle actin (α‐SMA) revealed significant coexpression suggesting endoMT. Treatment with H 2 S reduced oxidative stress, TGF‐β activation and inflammation. The expression of FSP‐1 and α‐SMA were decreased including the protein and mRNA levels of collagen. Our findings suggest that endoMT plays an important role in Ang‐II induced renal fibrosis in aged mice and inhibition of TGF‐β pathway by H 2 S therapy reduces endoMT thus preventing the progression of renovascular fibrosis. Grant Funding Source : HL104103