Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline.

ABSTRACT: Peripheral sensory neurons regenerate their axons after injury to regain function, but this ability declines with age. The mechanisms behind this decline are not fully understood. While excessive production of endothelin 1 (ET-1), a potent vasoconstrictor, is linked to many diseases that increase with age, the role of ET-1 and its receptors in axon regeneration is unknown. Using single cell RNA sequencing, we show that satellite glial cells (SGCs), which completely envelop the sensory neuron soma residing in the dorsal root ganglia (DRG), express the endothelin B receptor (ETBR), while ET-1 is expressed by endothelial cells. Inhibition of ETBR ex-vivo in DRG explant cultures improves axon growth in both adult and aged conditions. In vivo, treatment with the FDA-approved compo

SUBMITTER: Feng R 

PROVIDER: S-EPMC12157355 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature