Abstract: PO2459
Endoglin Is Upregulated in CKD and Is Associated with Increased Extracellular Matrix Production
Session Information
- CKD: Inflammation, Endothelial Dysfunction, and Signaling
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Gerrits, Tessa, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Dijkstra, Kyra L., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Bruijn, Jan A., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Baelde, Hans J., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Scharpfenecker, Marion, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
Group or Team Name
- Department of Pathology - Immunopathology group
Background
Chronic kidney disease (CKD) may result from any cause of renal dysfunction of sufficient magnitude, including diabetic nephropathy (DN) and different glomerulopathies like IgA nephropathy or focal segmental glomerulosclerosis (FSGS). Irrespective of the etiology, the common pathway in the pathophysiology of CKD involves glomerular sclerosis and tubulointerstitial fibrosis. TGF-β is an important cytokine in the development of renal fibrosis. Transmembrane glycoprotein endoglin, a TGF-β co-receptor could be a possible new therapeutic strategy to counteract the development of renal fibrosis in CKD.
Methods
Biopsies of patients with chronic kidney diseases including chronic allograft dysfunction (n=43), DN (n=11), FSGS (n=48), IgA nephropathy (n=85) and were selected; kidneys excluded for transplantation for technical reasons were used as controls (n=8). Sequential sections were stained for endoglin and Sirius Red. Human kidney fibroblasts were lentivirally transduced with either an empty vector or an endoglin knock-in construct and mRNA levels of genes involved in extra cellular matrix (ECM) production were measured with qPCR after TGF-β1 stimulation.
Results
The endoglin-positive area was significantly increased in the interstitium of patients with chronic allograft dysfunction, DN, FSGS and IgA-nephropathy compared to the controls (p<0.05). Endoglin-positive areas also co-localized with the Sirius Red-positive areas. The knock-in cell line showed an 7 times upregulation of the endoglin protein level compared to control cells. SERPINE-1 (p<0.05) and fibronectin (p<0.05) mRNA levels were significantly upregulated (respectively 2.5 and 2.8 times) after stimulation with TGF-β1 in endoglin overexpressing cells compared to controls.
Conclusion
Endoglin was upregulated in different chronic kidney diseases, which were characterized by interstitial fibrosis. We also showed that upregulation of endoglin increases TGF-β-dependent ECM production. This indicates that endoglin could be a potential target in reducing the development of fibrosis and offers an interesting opportunity to slow formation of fibrosis in CKD.