Fe3O4 magnetic nanoparticles ameliorate albumin-induced tubulointerstitial fibrosis by autophagy related to Rab7

Abstract Albuminuria is a primary feature in patients with CKD and an important contributor to tubulointerstitial fibrosis (TIF) development. Autophagy has been considered to be involved in renal tubular injury caused by albuminuria. Fe3O4 magnetic nanoparticles are related to many cellular activities, such as autophagy and inflammation. Rab7, a molecule involved in both endocytosis and autophagy, has been identified to protect renal tubular epithelial cells from albumin by regulating autophagy and MMP-2 activity in the early stage of albumin stimulation, but its role in the advanced stage is still unclear. Therefore, to investigate the effect of Fe3O4 magnetic nanoparticles on chronic renal tubular injury induced by excess albumin and to further determine the specific role of Rab7, we established a mouse model of TIF by intravenous injection of cationic bovine serum albumin (C-BSA) in Rab7-overexpressing transgenic mice. Our data revealed the decreased autophagy level, weakened MMP-2 activity and exacerbated renal tubular injury in these BSA-overloaded mice; furthermore, the degree of injury was more serious in Rab7-overexpressing transgenic mice. However, the application of Fe3O4 magnetic albumin nanoparticles (Fe3O4@BSA) enhanced MMP-2 activity and alleviated renal tubular injury, and these changes were mediated by an autophagy-dependent mechanism. Taken together, our results indicated that long-term albumin stimulation combined with overexpression of Rab7 could further decrease MMP-2 activity, exacerbate renal tubular injury and accelerate the development of TIF. Fe3O4@BSA could be a promising targeted tool for the management of CKD patients.