| First Author | Meng H | Year | 2023 |
| Journal | Front Cell Dev Biol | Volume | 11 |
| Pages | 1229788 | PubMed ID | 37576598 |
| Mgi Jnum | J:339076 | Mgi Id | MGI:7519408 |
| Doi | 10.3389/fcell.2023.1229788 | Citation | Meng H, et al. (2023) Evidence for developmental vascular-associated necroptosis and its contribution to venous-lymphatic endothelial differentiation. Front Cell Dev Biol 11:1229788 |
| abstractText | During development, apoptosis removes redundant cells and ensures proper organ morphogenesis. Necrosis is long known as an adult-bound inflammatory and pathologic cell death. Whether there exists physiological necrosis during early development has been speculated but yet clearly demonstrated. Here, we report evidence of necroptosis, a type of programmed necrosis, specifically in perivascular cells of cerebral cortex and skin at the early stage of development. Phosphorylated Mixed Lineage Kinase Domain-Like protein (MLKL), a key molecule in executing necroptosis, co-expressed with blood endothelial marker CD31 and venous-lymphatic progenitor marker Sox18. Depletion of Mlkl did not affect the formation of blood vessel network but increased the differentiation of venous-lymphatic lineage cells in postnatal cerebral cortex and skin. Consistently, significant enhancement of cerebrospinal fluid diffusion and lymphatic drainage was found in brain and skin of Mlkl-deficient mice. Under hypobaric hypoxia induced cerebral edema and inflammation induced skin edema, Mlkl mutation significantly attenuated brain-blood-barrier damage and edema formation. Our data, for the first time, demonstrated the presence of physiological vascular-associated necroptosis and its potential involvement in the development of venous-lymphatic vessels. |
