Figure 12

Schema showing the possible role of RAAS components in the glomerulo-tubular communication operating the pathogenesis of IgAN. Polymeric IgA from IgAN patients is capable of enhancing AngII release or Aldo synthesis through increasing the expression of ACE/ANG or CYP11B2 in HMC. The increased synthesis of AngII and Aldo up-regulates the TGF-β synthesis via binding to their respective receptors: AT1R and MR. Aldo is able to further up-regulate the ACE/ANG expression and AngII release in HMC whereas AngII increases the Aldo release by HMC via increased expression of CYP11B2. This vicious cycle involving pIgA-induced AngII and Aldo in HMC amplifies the pIgA-induced HMC damages and initiates the downstream inflammatory cascade in PTEC through the glomerulo-tubular communication. AngII released by pIgA-activated HMC up-regulates the expression of AT2R and MR by PTEC. Binding of AngII and Aldo to their respective receptors on PTEC induces cellular apoptosis through increased NADPH activity and generation of ROS. Combined blockade of AT2R and MR can prevent pIgA-induced PTEC apoptosis through these glomerulo-tubular communications.