Abstract: SA-PO238

Nephronectin Is a Component of Novel Glomerular Adhesions That Regulate Mesangial Adhesion and Behavior

Session Information

  • Glomerular: Cell Biology
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Glomerular

  • 1003 Glomerular: Cell Biology

Authors

  • Hiremath, Chitkale, University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Marciano, Denise K., University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

Defects in the glomerular basement membrane (GBM) cause heritable glomerular disease and are associated with the majority of acquired glomerular diseases, although their role in pathogenesis of the latter is unclear. The GBM contacts all cells of the glomerular tuft, namely podocytes, endothelia, and mesangial cells, whose function is coordinated to form an integrated filtration unit. Much of the GBM is deposited between podocytes and endothelia, where it is well known to form a critical part of the permeability barrier. However, the GBM also interacts directly with mesangial cells. Currently, little is known of specific GBM-mesangial interactions and their role in glomerular development, maintenance, and disease.

Methods

We utilize several mouse models in this study including conditional deletion of Npnt, the gene encoding nephronectin, using the Six2-cre line and Podocin-cre line.

Results

We find nephronectin, a GBM component and known ligand of α8β1 integrin, is produced by podocytes and deposited into the GBM, where it is required for formation of a novel GBM-mesangial cell adhesion structure. These specialized adhesions occur at sites of mesangial cell protrusion that are highly enriched in α8β1 integrin and appear to anchor capillary loops. Absence of nephronectin disrupts these adhesion structures, leading to mislocalization of α8β1, a pronounced increase in mesangial cell number, and mesangial sclerosis.

Conclusion

These results demonstrate a novel role for nephronectin-α8β1 integrin in a newly described adhesion complex.

Funding

  • NIDDK Support