Fig. 9: Working model: The myeloid Mas-PKM2-Spi1 lactylation axis promotes MASLD progression and is targeted by MM@NP-TFDG. | Signal Transduction and Targeted Therapy

Fig. 9: Working model: The myeloid Mas-PKM2-Spi1 lactylation axis promotes MASLD progression and is targeted by MM@NP-TFDG.

From: Myeloid Mas drives pyruvate kinase M2-mediated Spi1 lactylation to fuel inflammatory senescence in MASLD

Fig. 9: Working model: The myeloid Mas-PKM2-Spi1 lactylation axis promotes MASLD progression and is targeted by MM@NP-TFDG.The alternative text for this image may have been generated using AI.

The Mas-PKM2 interaction in myeloid cells stabilizes PKM2 dimers, promoting its nuclear translocation. Nuclear PKM2 facilitates lactate-dependent lactylation of Spi1 at K208, enhancing its transcriptional activity at SASP gene promoters (e.g., TNF-α, IL-6). This axis drives glycolytic reprogramming, promotes differentiation of FN1+ monocyte precursors into pro-inflammatory macrophages and sustains senescence-associated inflammation, thereby accelerating MASLD. The macrophage-membrane-coated nanoparticle MM@NP-TFDG selectively delivers the Mas-binding compound TFDG to hepatic macrophages, disrupting the Mas-PKM2 interaction and ameliorating disease pathology

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