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

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.