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Figure 8
(A) Diagram of RV formation process. During nephron regeneration, renal progenitor cells (RPCs) congregate to form cell aggregate, then renal interstitial cells (RICs) form a network to wrap the RPC aggregate and secrete PGE2. RIC-secreted PGE2 and RPC-secreted Wnt4a synergistically promote RPCs to proliferate rapidly and then differentiate into RV. (B) Model of the interaction between PGE2 and Wnt signaling pathway in RPC during regeneration. During nephron regeneration, RICs that are in close contact with RPC aggregates express Cox2a and secrete PGE2. PGE2 signaling interacts with Wnt/β-catenin pathway at the level of β-catenin destruction complex and direct modification of β-catenin stability in RPC. This is achieved through EP4b induction and the activation of PKA. PKA phosphorylates GSK3β at Ser9, preventing the assembly of the β-catenin destruction complex. PKA also phosphorylates β-catenin at Ser675, resulting in stabilization of β-catenin. Wnt4a secreted by RPC can also reduce the stability of the destruction complex through the FZD receptor, thereby enhancing stabilization of β-catenin in response to acute kidney injury (AKI).
Graphical abstract summarizing the research findings.