Metabolic reprogramming by microvesicle restores glycolysis and rescues nerve injury-induced erectile dysfunction via endogenous S1P-mediated MEK/ERK signaling
Source abstract
Abstract
Cavernous nerve injury-induced erectile dysfunction (CNI-ED) lacks therapies that directly promote nerve regeneration. Here, we show that microvesicle (MV) derived from well differentiated PC12 cells restore erectile function in a rat CNI model by reprogramming local energy metabolism. Local administration of MV to the injured nerve elevated ATP levels, reduced neuronal apoptosis and increased intracavernous pressure. Mechanistically, MV were enriched in sphingosine-1-phosphate (S1P), which activated S1PR1 and downstream MEK1/2-ERK1/2 signaling, leading to upregulation of glycolytic enzymes (Glut3, HK2, MCT4, LDHA) and enhanced glycolytic flux. Knockdown of SphK1 in donor cells depleted S1P from MV and abolished both metabolic and regenerative effects. Our data identify an S1P-S1PR1-MEK/ERK-glycolysis axis that drives nerve regeneration and nominate neuron-derived MV as a metabolism-targeted therapeutic strategy for CNI-ED.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Sexual function and dysfunction studies · Extracellular vesicles in disease · Phosphodiesterase function and regulation
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
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