ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO420

Endoglin as Potential Target to Slow Down Progressive Diabetic Nephropathy via Inhibition of Fibrosis Formation

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Gerrits, Tessa, LUMC, Leiden, Netherlands
  • Zandbergen, Malu, LUMC, Leiden, Netherlands
  • Bruijn, Jan A., Leiden University Medical Center, Dept.Pathology, Leiden, Netherlands
  • Baelde, Hans J., Leiden University Medical Center, Leiden, Netherlands
  • Scharpfenecker, Marion, Leiden University Medical Center, Leiden, Netherlands
Background

Diabetic nephropathy (DN) is a complication of diabetes, resulting in progressive decline of renal function and proteinuria. Progressive DN is histologically characterized by glomerular matrix expansion and interstitial fibrosis, in which TGF-β plays an important role.
Endoglin, a co-receptor of TGF-β, mostly known for regulating endothelial cell functions, is also described in human fibrotic tissues such as liver, heart and intestine. To investigate the role of endoglin in progressive DN, we measured endoglin expression in biopsies of patients with DN and characterized the endoglin-expressing cell type in the interstitium. We also investigated the effect of endoglin knockdown on extracellular matrix production in kidney fibroblasts in vitro.

Methods

Kidney biopsy material of 11 patients with DN was collected. As control, tumor free tissue of 7 patients with a renal tumor was used. Sequential sections were stained for endoglin and Sirius Red. The positively stained interstitial area was quantified using ImageJ. Immunofluorescent double stainings for endoglin and CD31, CD68, vimentin or a-SMA were performed on biopsy material from a patient with and without DN. A human kidney fibroblast cell line (TK173) was transduced with a lentiviral vector expressing an shRNA against endoglin.

Results

Endoglin was significantly upregulated in patients with DN compared to controls (p<0.001). Also, the Sirius red-positive area was significantly increased in patients with DN (p<0.001). Immunofluorescence showed co-expression of endoglin with the endothelial marker CD31. Endoglin also co-localized with the myofibroblast marker a-SMA. Co-localization with fibroblast (vimentin) or macrophage (CD68) markers was not observed. In cell culture, endoglin knockdown in fibroblast resulted in reduced PAI-1, CTGF and fibronectin expression after stimulation with TGF-β (p<0.05).

Conclusion

Endoglin is upregulated in the interstitium of DN patients and is expressed in myofibroblasts. In vitro, endoglin is involved in TGF-β dependent matrix production. Therefore, endoglin might play a role in the development of fibrosis and thus the progression towards end-stage renal disease in DN.