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Kidney Week

Abstract: PO1275

Uncovering the Role of the Extracellular Matrix in ADPKD Progression

Session Information

Category: Genetic Diseases of the Kidneys

  • 1001 Genetic Diseases of the Kidneys: Cystic


  • Pellegrino, Elisa, Universita Vita Salute San Raffaele, Milano, Lombardia, Italy
  • Steidl, Maria Elena, Universita Vita Salute San Raffaele, Milano, Lombardia, Italy
  • Chiaravalli, Marco, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Boletta, Alessandra, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy
  • Nigro, Elisa Agnese, IRCCS Ospedale San Raffaele, Milano, Lombardia, Italy

Polycystic Kidney Disease (PKD) is a genetic disorder due to mutation in either Pkd1 or Pkd2 genes and characterized by bilateral cysts formation.
We recently uncovered a direct role of PC-1, the protein product of Pkd1 gene as a mechanosensor of extracellular stiffness. We found that PC-1 interactors mediate inhibition of actomyosin contraction that mediates the cellular response to the rigidity of the Extracellular Matrix (ECM). Based on these findings we speculated that Pkd1-/- cells fail to properly respond to the extracellular mechanical force of ECM leading to excessive matrix deposition and proliferation. In line with this, kidneys of end-stage PKD patients show enhanced fibrosis typical of cystic kidney disease and tumors.
We then wondered whether PKD ECM is a part of an active Cyst Microenvironment (CME), exerting a key role in the evolution of the disease.


We characterized CME in the renal tissue of an aggressive Pkd1ΔC/flox:Ksp-Cre and a low progressive Pkd1ΔC/flox:Tam-Cre inducible mouse models.
To study the composition and the mechanical properties of the cystic ECM we decellularized cystic kidneys obtaining ECM-derived kidney scaffolds. Furthermore, we isolated matrix from Pkd1-/- fibroblasts in vitro.


We have characterized the renal tissue microenvironment of two Pkd1 inducible mouse models at a late stage of the disease confirming the presence of fibrosis, immune infiltrates and progressive accumulation of collagen I. In line with an active role played by fibroblasts in the deposition and remodeling of the ECM, our data showed the presence of activated fibroblasts in cystic kidneys.
We performed a proteomic analysis of cystic kidney scaffolds by Mass Spectrometry (MS). Cluster analysis of MS data showed a clear separation between cystic and control scaffolds.
Finally we found that matrix isolated from Pkd1-/- cells was able to influence differently key cellular properties such as adhesion, polarization, proliferation and migration.


ECM plays an active role in the progression of ADPKD disease.