Aluminum exposure induces nephrotoxicity via fibrosis and apoptosis through the TGF-β1/Smads pathway in vivo and in vitro

Abstract

solution at 0, 5, 10, and 20 mg/(kg·d), respectively, for 4 weeks. The kidney function of rats and Al contents in the kidney were measured, and the pathological structural changes and apoptosis of the kidney were observed. Meanwhile, the expression of fibrosis- and apoptosis-related proteins was detected with western blot. For the in vitro assay, HK-2 cells were used to construct a model to evaluate the effects of Al exposure on cell viability, cell apoptosis, and the expression of fibrosis- and apoptosis-related proteins. Additionally, the TGF-β1/Smads pathway was also altered in HK-2 cells, followed by the measurement of changes in apoptosis and fibrosis-related proteins. The results revealed that Al could accumulate in kidney tissues, then leading to histopathological changes and kidney function impairment, promoting renal tubular cell apoptosis and renal collagen fiber deposition, and also elevating the expression of TGF-β1/Smads pathway-related proteins. In vitro experiments also exhibited that Al exposure increased apoptosis and the expression of fibrosis-related factors in HK-2 cells, accompanied by activation of the TGF-β1/Smads pathway. Further modulation of the TGF-β1/Smads pathway manifested that activation of the TGF-β1/Smads pathway facilitated Al-induced apoptosis and fibrosis-related factor expression, while inhibition of the pathway negated this effect of Al. In conclusion, the findings of the present study illustrate that Al exposure damages kidney function and facilitate apoptosis and kidney fibrosis, which may be achieved through the activation of the TGF-β1/Smads pathway. This study provides a new theoretical basis for the study of nephrotoxicity induced by excessive Al exposure.