What question did this study set out to answer?

The aim is to explore the multifunctional roles of PEDF signaling in retinal development and associated diseases.

May 11, 2026Communications Biology0 citationsOpen Access

Complexity of PEDF multifunctional signaling in retinal development and diseases

ZYZihao Yu MZMingliang Zhang CRChangjie Ren

Key Points

The aim is to explore the multifunctional roles of PEDF signaling in retinal development and associated diseases.
Utilized siRNA and pharmacological inhibition to define receptor-specific signaling.
Analyzed receptor expression patterns in retinoblasts during retinal maturation.
Investigated PEDF-induced signaling pathways in HUVEC and ARPE-19 cells.
PEDF activates AKT, STAT3, ERK, and p38 while suppressing β-catenin in HUVECs.
LR couples PEDF to STAT3 and β-catenin in HUVECs; in ARPE-19 cells, it links PEDF to AKT/STAT3/ERK.
A PEDF mimetic (Ppx) replicates these signaling effects.

Abstract

retinas, and define receptor-specific signaling using siRNA and pharmacological inhibition. These receptors are broadly expressed in retinoblasts and acquire cell-type-specific patterns during retinal maturation via PEDF-independent mechanisms. LR and LRP6 also colocalize at the outer limiting membrane (OLM). Functionally, PEDF activates AKT, STAT3, ERK, and p38 and suppresses β-catenin in both HUVEC and ARPE-19 cells, while mTOR activation remains receptor-independent. LR and LRP6 couple PEDF to STAT3 and β-catenin in HUVECs, whereas in ARPE-19 cells LR links PEDF to AKT/STAT3/ERK and LRP6 to AKT/β-catenin. ATGL inhibition abolishes PEDF-induced AKT/STAT3/ERK/p38 signaling in both cell types. A 17-mer PEDF mimetic (Ppx) recapitulates these effects. These findings help define a framework for PEDF pleiotropy and highlight the OLM as a therapeutic interface.

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