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Kidney Week

Abstract: PO0663

Contribution of Endothelial ADAM17 in a Pre-Diabetic Mouse Model

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Palau, Vanesa, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Jarrín, Javier Josué, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Calle, Sofia Villanueva, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Márquez, Eva, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Rodriguez, Eva, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Crespo, Marta, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Soler, Maria Jose, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Pascual, Julio, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Barrios, Clara, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
  • Riera, Marta, Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Catalunya, Spain
Background

ADAM17 activates inflammatory and fibrotic processes through the shedding of various molecules such as TNF-α or TGF-α. In physiological situations, ADAM17 is expressed mainly in the distal tubular cell while, in renal damage, its expression increases throughout the kidney including the endothelium. Galectin 3 (Gal3) is a lectin that is postulated as a biomarker of kidney damage. Its overexpression in diabetic nephropathy could be a compensatory mechanism for damage induced by reactive oxygen species (ROS).
To characterize, for the first time, an experimental mice model fed with high-fat diet (HFD) with deletion of ADAM17 in endothelial cells and to describe the expression of kidney Gal3.

Methods

After 25 weeks of HFD, glycaemia, glucose tolerance, body weight, albuminuria, glomerular microscopy (PAS staining) and Gal3 (immunohistochemistry) were analyzed in 15 wildtype (WT) mice and 15 endothelial ADAM17-KO mice.

Results

HFD mice had higher glucose levels, glucose intolerance, and higher body weight compared to standard diet (SD) mice. Moreover, HFD increased albumin/creatinine ratio in WT mice compared to ADAM17-KO mice. At the glomerular level, WT mice with HFD had bigger glomerular size and mesangial matrix expansion. In contrast, the deletion of ADAM17 prevented the increase in glomerular size and decreased the mesangial area and index. Gal3 increased its expression in ADAM17-KO mice on both SD and HFD mice (see table).

Conclusion

The deletion of ADAM17 in endothelium prevents the appearance of glomerular hypertrophy, expansion of the mesangial matrix, albuminuria and increases the expression of Galectin-3 in the renal cortex. The increase in the expression of Galectin-3 could be a compensatory mechanism for the lack of activation of the EGFR / TNFR pathway in the endothelium ADAM17-KO model.