Abstract
Podocyte injury is the main cause of proteinuria in lupus nephritis (LN). Nestin, an important cytoskeleton protein, is expressed stably in podocytes and is associated with podocyte injury. However, the role of nestin in the pathogenesis of proteinuria in LN remains unclear. The correlations among nestin, nephrin and proteinuria were analyzed in LN patients and MRL/lpr lupus-prone mice. The expression of nestin in mouse podocyte lines (MPCs) and MRL/lpr mice was knocked down to determine the role of nestin in podocyte injury. Inhibitors and RNAi method were used to explore the role of mitophagy and oxidative stress in nestin protection of podocyte from damage. There was a significantly negative correlation between nestin and proteinuria both in LN patients and MRL/lpr mice, whereas the expression of nephrin was positively correlated with nestin. Knockdown of nestin resulted in not only the decrease of nephrin, p-nephrin (Y1217) and mitophagy-associated proteins in cultured podocytes and the podocytes of MRL/lpr mice, but also mitochondrial dysfunction in podocytes stimulated with LN plasma. The expression and phosphorylation of nephrin was significantly decreased by reducing the level of mitophagy or production of reactive oxygen species (ROS) in cultured podocytes. Our findings suggested that nestin regulated the expression of nephrin through mitophagy and oxidative stress to protect the podocytes from injury in LN.
Highlights
Long-term severe proteinuria is one of the main clinical manifestations of lupus nephritis (LN), one of the most severe and frequent complication of systemic lupus erythematosus (SLE), and a sign of poor prognosis[1]
Nestin contributed to the proteinuria formation by regulating nephrin in lupus nephritis Our previous study has proved that abnormal nestin expression played an important role in regulating proteinuria in diabetic nephropathy[11]
These results indicated that nestin and nephrin might be related to the proteinuria that was involved in the pathogenesis of LN
Summary
Long-term severe proteinuria is one of the main clinical manifestations of lupus nephritis (LN), one of the most severe and frequent complication of systemic lupus erythematosus (SLE), and a sign of poor prognosis[1]. The patients with LN have varying degrees of renal injury and proteinuria, and proteinuria levels are unstable in the LN patients, which are associated with a strong selfrenewal and repair system of the glomerular filtration membrane[2]. In the early LN, it is possible to repair the pathological damage to filtration membrane caused by patients. In a variety of distinct mechanisms of proteinuria, the podocytes dysfunction or injury is the most important cause[4,5]. Knocking out the expression of nestin in mice podocytes could cause extensive disappearance or fusion of the foot processes[9]. The expression of nestin protein in the glomerular podocytes increased transiently and decreased followed by increased proteinuria while the wistar rats were injected with aminonucleoside puromycin (PAN)[10].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
