Abstract: TH-PO0304
Tenascin-C Controls Migration and Proliferation of Parietal Epithelial Cells and Glomerulosclerosis Progression
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Sun, Ke, Department of Nephrology, Zhejiang University Medical College Affiliated Sir Run Run Shaw Hospital, Hangzhou, China
- Hao, Chuan-Ming, Huashan Hospital Fudan University, Shanghai, China
Background
The pathogenesis of the development of sclerotic lesions in focal segmental glomerulosclerosis (FSGS), especially the mechanism of parietal epithelial cells (PECs) invading glomerular capillaries and promoting kidney failure, is poorly characterized. Increasing evidence supports the notion that the activation of PECs is seen as an early event in FSGS, further study to identify new mechanism re still urgently needed. The present study aimed to explore the role of Tenascin (TNC), an extracellular matrix glycoprotein, in the activation of PECs and the pathogenesis of FSGS.
Methods
A TNC promoter driven tamoxifen inducible CreER2-IRES-EGFP knock-in mouse line (BalbC) was generated to examine the role of TNC in FSGS. TNC-CreER-tdTamato mice were used for a TNC reporter and cell lineage tracing experiment. And we also evaluate the effect of TNC on the migration and proliferation of PECs.
Results
In vivo, TNC was selectively expressed in the PECs under physiological condition in TNC-CreER-tdTomato mice, which was significantly induced to express in kidney of adriamycin-induced FSGS as shown by immunoblot and RT-qPCR. Immunohistochemistry revealed that the expression of TNC was localized to the sclerotic area in the glomeruli and in the adhesion between the glomerular tuft and Bowman’s capsule. Importantly the expression of TNC was also observed in sclerotic area of FSGS patients and the expression of TNC in the PECs was also observed by in situ hybridization. And cell lineage tracing experiments suggested the migration and invasion of the PECs into the glomerular tufts during FSGS. In vitro, PECs were activated, migrated, and proliferated after TNC treatment. Significantly, TNC deletion significantly attenuated the proportion of glomerulosclerosis, kidney function and proteinuria in adriamycin-induced FSGS. Meanwhile, TNC deletion attenuated the migratory and proliferative phenotype of PECs. Furthermore, we demonstrated that TNC promoted the migration of PECs by activating Integrin β1/FAK/SRC signaling and promoted the proliferation of PECs by activating EGFR/ERK signaling.
Conclusion
The expression of TNC is a critical pathogenic switch driving the PEC phenotype in FSGS, and provide a potential therapeutic avenue for the treatment of this disease.
Acknowledgment
This work was supported by National Science Foundation of China Grants 82400852.
Funding
- Government Support – Non-U.S.