Figure 1.

Hypothetical model for changes in the ECM environment of the proximal tubule following loss of VHL. (A) VHL controls the half-life of integrins that apply force to fibronectin molecules associated with the basement membrane, which regulates their fibrillogenesis. VHL also suppresses expression of matrix metallopeptidases (MMPs) and upregulates tissue inhibitors of metalloproteinases (TIMPs), ensuring integrity of the basement membrane. (B) Following inactivation of VHL, fibronectin fibrillogenesis is reduced and MMPs become active, degrading the basement membrane and promoting angiogenesis.