Tenascin-C Promotes Migration and Proliferation of Parietal Epithelial Cells and Participates in the Pathogenesis of FSGS
- Glomerular Diseases: Mechanisms of Cellular Injury
November 05, 2022 | Location: W414, Orange County Convention Center‚ West Building
Abstract Time: 04:30 PM - 04:39 PM
Category: Glomerular Diseases
- 1301 Glomerular Diseases: Fibrosis and Extracellular Matrix
- Sun, Ke, Fudan University, Shanghai, Shanghai, China
- Hao, Chuanming, Fudan University, Shanghai, Shanghai, China
The parietal epithelial cells (PECs) have been suggested to play an important role in FSGS. Our previous study shows that extracellular matrix Tenascin-C (TNC) is expressed in the PECs. The present study examined the role of TNC expressing PECs and TNC in the pathogenesis of FSGS.
Experimental FSGS was induced on 8-week-old male BalbC mice by i.v. of 10.5 mg/kg body weight of adriamycin. 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.
TNC reporter mice showed that TNC was selectively expressed in the PECs. The TNC expression was induced in the kidney of adriamycin-induced FSGS as shown by immunoblot. 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 of sclerotic lesions. Importantly the expression of TNC in the PECs was also observed in human kidney by in situ hybridization.
To examine the role of TNC expressing parietal epithelial cells in sclerosis lesion in FSGS, we did a cell lineage tracing study. Following adriamycin injection, the daughter cells of the TNC expressing PEC lineage appeared in in glomerular tufts, suggesting the migration and invasion of the PECs into the glomerular tufts.
To further examine the role of TNC in the sclerotic damage in FSGS, we generated TNC knockout mice. BUN was significantly increased in mice following adriamycin treatment ((6.71±0.73) vs(18.38±2.93) mmol/l, p<0.01). TNC deletion significantly attenuated the elevation of BUN ((15.42±2.09) mmol/l, p<0.05). TNC deletion also significantly attenuated the proteinuria following adriamycin treatment (p<0.05). Cell culture studies showed that TNC promoted PEC proliferation and migration. EGFR/ERK cascade and intergrin β1 signaling mediated the effect of TNC on PEC.
TNC plays an important role in promoting the migration of parietal epithelial cells into the sclerotic area of the glomeruli and participates in the pathogenesis of FSGS.