We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mechanism and restoration strategy of lysosomal abnormalities induced by urinary protein overload in proximal tubule epithelial cells.
- Authors
Li, Xiaoyu; Zou, Ting; Wang, Shujun; Wu, Hongluan; Wu, Man; Liu, Zejian; Liu, Huafeng
- Abstract
Background: Persistent elevated concentrations of urinary protein can destroy proximal tubule epithelial cells (PTECs) by inducing lysosomal abnormalities, thereby aggravating PTEC damage and renal fibrosis. However, the specific mechanisms of these serial biochemical events and methods for treating or preventing PTEC damage upon proteinuria need further investigation. Results: In this study, electron microscopy and dual‐labeled immunofluorescence analysis for identifying lysosome type revealed inadequate primary lysosome biogenesis and secondary lysosome accumulation in the PTECs of patients with minimal change nephrotic syndrome or membranous nephropathy who suffered from proteinuria. In vitro studies on HK‐2 cells indicated that this abnormality was associated with decreased expression of transcription factor EB (TFEB). In contrast, TFEB overexpressing HK‐2 cells under urinary protein overload exhibited significantly reduced accumulation of secondary lysosomes and increased proportion and quantity of primary lysosomes as indicated by dual‐labeled immunofluorescence. Further, these cells could upregulate lysosomal degradation functions, as determined using Cathepsin L activity assays and flow cytometry for dye quenched‐albumin. Conclusions: These results indicate that abnormal TFEB expression is a key mechanism of lysosomal dyshomeostasis caused by protein overload in PTECs. TFEB is thus a potential therapeutic target for the treatment of urinary protein‐related kidney disease. Key Findings: Proteinuria destroys proximal tubule epithelial cells (PTECs) via lysosomal damage.TFEB expression in PTECs is decreased upon urinary protein treatment.TFEB overexpression PTECS prevents the lysosomal damage caused by urinary protein.TFEB is thus a therapeutic target for urinary protein‐related renal disease.
- Subjects
EPITHELIAL cells; RENAL fibrosis; TRANSCRIPTION factors; PROTEINS; HUMAN abnormalities; KIDNEY diseases
- Publication
Developmental Dynamics, 2021, Vol 250, Issue 7, p943
- ISSN
1058-8388
- Publication type
Article
- DOI
10.1002/dvdy.297