Abstract: TH-PO754
Podocyte Injury Induces Rapid Collagen Degradation Within Mesangial Cells
Session Information
- Glomerular Diseases: Podocyte Biology - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1403 Podocyte Biology
Author
- Matsusaka, Taiji, Tokai Daigaku Igakubu Daigakuin Igaku Kenkyuka, Isehara, Kanagawa, Japan
Background
Glomerulosclerosis, characterized by accumulation of extracellular matrix (ECM) proteins, is primarily caused by podocyte injury. In our investigation of mouse model of podocyte injury, we frequently observed mesangiolysis in sclerotic glomeruli. Our hypothesis is that mesangial collagen undergo degradation subsequent to podocyte injury. This study aimed to characterize the process of collagen degradation following podocyte injury.
Methods
Podocyte injury was induced in transgenic mice expressing hCD25 in podocytes through the injection of hCD25-directed immunotoxin, LMB2. Denatured collagen was visualized using Collagen hybridizing peptide (CHP), a specific binder of unfolded collagen chains, and imaged with LSM880. Collagenolytic activities was assessed by quenched fluorogenic DQ-Gelatin or DQ-Collagen IV.
Results
CHP staining was intensified in glomeruli seven days after the induction of podocyte injury preceding the establishment of sclerotic lesions. The intensity of glomerular CHP staining correlated with the severity of glomerular injury and was localized in mesangial cells labeled by Itga8. Notably, intense glomerular CHP staining was absent in decellularized sections, while hydroxyproline (HP) staining persisted (Figure). The primary CHP staining was partially co-localized with MEK1/2 or GAPDH, but not with LAMP1, a lysosome marker, or with ERp72, an ER marker, suggesting that CHP is present in the cytoplasm. Collagenolytic activity in glomeruli with podocyte injury was found to be elevated in parallel with CHP staining.
Conclusion
These findings indicate that podocyte injury triggers and promotes degradation of collagen and accumulation of denatured collagen within mesangial cells. Further investigation is required to elucidate the detailed process involved.
Figure
Funding
- Government Support – Non-U.S.