<p>CD248 is a pericyte marker during embryonic and tumor neovascularization. Although its expression pattern and function in mammalian pericytes have been extensively studied, its role in zebrafish pericytes remains largely unexplored. In this study, we identify that among the two zebrafish orthologs of human CD248, <i>cd248a</i>, rather than <i>cd248b</i>, is predominantly expressed in pericytes during embryonic development. We generate <i>cd248a</i> and <i>cd248b</i> mutant zebrafish (<i>cd248a</i><sup>cc11/cc11</sup> and <i>cd248b</i><sup>cc12/cc12</sup>) and observe a significant reduction in pericyte numbers in <i>cd248a</i><sup>cc11/cc11</sup> mutants, accompanied by disruption of the blood-brain barrier. Notably, treatment with AG1295, a platelet-derived growth factor receptor inhibitor, attenuates the increase in pericyte proliferation induced by <i>cd248a</i> overexpression. Additionally, we find that CoCl<sub>2</sub>-induced pericyte apoptosis is enhanced in <i>cd248a</i><sup>cc11/cc11</sup> larvae, indicating that <i>cd248a</i> provides protection against hypoxia-induced apoptosis. Taken together, our findings elucidate the role and underlying mechanisms of <i>cd248a</i> in regulating pericyte proliferation and apoptosis in zebrafish.</p>

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Cd248a regulates pericyte development and viability in zebrafish

  • Chao Wang,
  • Yinming Zhong,
  • Yi Zhang,
  • Yiyang Jiang,
  • Chenshiyu Wang,
  • Lele An,
  • Chunhua Luo,
  • Lan Yang,
  • Zhicheng He,
  • Ying Yang,
  • Min Luo,
  • Min Mao,
  • Wenying Wang,
  • Qing Liu,
  • Yu Shi,
  • Yi-Fang Ping

摘要

CD248 is a pericyte marker during embryonic and tumor neovascularization. Although its expression pattern and function in mammalian pericytes have been extensively studied, its role in zebrafish pericytes remains largely unexplored. In this study, we identify that among the two zebrafish orthologs of human CD248, cd248a, rather than cd248b, is predominantly expressed in pericytes during embryonic development. We generate cd248a and cd248b mutant zebrafish (cd248acc11/cc11 and cd248bcc12/cc12) and observe a significant reduction in pericyte numbers in cd248acc11/cc11 mutants, accompanied by disruption of the blood-brain barrier. Notably, treatment with AG1295, a platelet-derived growth factor receptor inhibitor, attenuates the increase in pericyte proliferation induced by cd248a overexpression. Additionally, we find that CoCl2-induced pericyte apoptosis is enhanced in cd248acc11/cc11 larvae, indicating that cd248a provides protection against hypoxia-induced apoptosis. Taken together, our findings elucidate the role and underlying mechanisms of cd248a in regulating pericyte proliferation and apoptosis in zebrafish.