Peripheral mural cell recruitment requires cell-autonomous heparan sulfate
| Autor: | Holger Gerhardt, Yu Yamaguchi, Emma Nye, Ralf H. Adams, Maya H. Nisancioglu, Denise Stenzel |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Central Nervous System
Platelet-derived growth factor Endothelium medicine.medical_treatment Immunology Neovascularization Physiologic Mice Transgenic N-Acetylglucosaminyltransferases Biochemistry Mural cell Receptor Platelet-Derived Growth Factor beta chemistry.chemical_compound Mice Growth factor receptor Cell Movement medicine Cell Adhesion Animals biology Growth factor Endothelial Cells Cell Biology Hematology Heparan sulfate Embryo Mammalian Cell biology Mice Inbred C57BL Autocrine Communication medicine.anatomical_structure chemistry Blood vessel maturation cardiovascular system biology.protein Blood Vessels Heparitin Sulfate Platelet-derived growth factor receptor Gene Deletion |
| Zdroj: | Blood. 114(4) |
| ISSN: | 1528-0020 |
| Popis: | Blood vessel maturation and stability require recruitment of mural cells (MCs) to the nascent vessel. Loss or detachment of MCs causes vascular dysfunction in diseases. N-sulfation of heparan sulfate (HS) is required for platelet-derived growth factor B (PDGF-B) retention and platelet-derived growth factor receptor-β (PDGFR-β) signaling during MC recruitment. To analyze the specific role of MC-derived HS in this process, we inactivated HS synthesis in MCs. MC-specific loss of HS causes embryonic lethality associated with vascular patterning defects, edema, and hemorrhages during late gestation. MC recruitment in the skin is impaired, correlating with defective PDGFR-β and transforming growth factor-β (TGF-β)–SMAD signaling. Accumulation of rounded cells positive for MC markers close to the vessels indicates defective polarization and migration of local MC progenitors. In contrast, MC recruitment and signaling in the central nervous system (CNS) are unaffected by MC HS loss. Our results suggest that HS is selectively required in a cell-autonomous manner, acting in cis with PDGFR-β and TGF-β receptors during induction/polarization and migration of local progenitor cells to the nascent vessel. Once MCs are in contact with the vessel, as during CNS vascularization, endothelial HS appears sufficient to facilitate PDGFR-β activation in trans. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|