Abstract: SA-PO730
Endoglin Promotes Interstitial Fibrosis in CKD
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Gerrits, Tessa, Leiden University Medical Center, Leiden, Netherlands
- Berkhoff, Meilin, Leiden University Medical Center, Leiden, Netherlands
- Brouwer, Isabella Johanna, Leiden University Medical Center, Leiden, Netherlands
- Bruijn, Jan A., Leiden University Medical Center, Leiden, Netherlands
- Baelde, Hans J., Leiden University Medical Center, Leiden, Netherlands
- Scharpfenecker, Marion, Leiden University Medical Center, Leiden, Netherlands
Background
Tubulointerstitial fibrosis is a common process leading to chronic renal damage. It is characterized by extracellular matrix (ECM) deposition and pathological scar formation driven by transforming growth factor beta (TGF-β). Inhibiting excessive ECM production could be a strategy to reduce the functional decline of the kidney and thereby the progression towards end-stage renal disease. Endoglin, a co-receptor of the TGF-β-receptor, could be an interesting target to inhibit fibrosis formation.
Methods
Biopsies of patients with kidney diseases characterized by interstitial fibrosis, such as focal segmental glomerular sclerosis (FSGS; n=48), diabetic nephropathy (DN; n=11) and chronic allograft dysfunction (CAD; n=43) were selected; healthy kidneys were used as controls (n=8). Sections were stained for endoglin and the positively-stained area was measured. DN and CAD sequential sections were stained for Sirius Red, a marker for interstitial fibrosis. Endoglin mRNA expression in whole kidney tissue of another DN cohort (n=23) was measured with qPCR; healthy kidneys were used as controls (n=12). Lastly, collagen type I production was measured with western blot in TGF-β stimulated lentivirally transduced fibroblasts that were either wild type or knock down for endoglin.
Results
Endoglin was increased in the interstitium of patients with FSGS, DN and chronic allograft dysfunction compared to controls (p<0.001). The endoglin-positive area colocalized with the Sirius Red-positive area. qPCR showed upregulation of endoglin mRNA in patients with DN compared to healthy controls (p<0.05). The western blot analysis demonstrated that collagen type I production after TGF-β stimulation was less upregulated in the endoglin knockdown fibroblasts compared to wild type fibroblasts.
Conclusion
We show that endoglin is overexpressed in different patient cohorts with interstitial kidney fibrosis and that it colocalizes with Sirius Red-positive areas. We also show that lowering endoglin levels reduces TGF-β-induced collagen type I production. These results suggest that endoglin could be a potential target reduce the development of fibrosis. This offers an interesting opportunity to treat patients with declining renal function.