Epigenetic reprogramming via EZH2 inhibition rescues fibroadipose pathogenesis in secondary lymphedema through activating PPARγ signaling.

ABSTRACT:

Background

Secondary lymphedema, a progressive disorder characterized by pathological fibroadipose tissue accumulation, is a common problem after cancer treatment and orthopedic surgery. It remains a therapeutic enigma due to its self-perpetuating fibrotic cascade and lack of disease-modifying therapies. While current therapeutic approaches focus on symptom management and volume reduction, they don't address the epigenetic reprogramming driving fibrotic commitment-a process recently linked to enhancer of zeste homolog 2 (EZH2). Although EZH2 inhibitor EPZ6438 has been approved for clinical application, its therapeutic potential in fibroadipose pathogenesis remains unexplored, leaving a critical gap in understanding epigenetic factors in lymphedema progression.

Methods

Human

SUBMITTER: Chen Z 

PROVIDER: S-EPMC12514517 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature