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Decreased blood vessel density and endothelial cell subset dynamics during ageing of the endocrine system
The EMBO Journal ( IF 9.4 ) Pub Date : 2020-11-20 , DOI: 10.15252/embj.2020105242
Junyu Chen 1, 2 , Luciana Lippo 1 , Rossella Labella 1 , Sin Lih Tan 1 , Brian D Marsden 3, 4 , Michael L Dustin 3 , Saravana K Ramasamy 5, 6 , Anjali P Kusumbe 1
Affiliation  

Age‐associated alterations of the hormone‐secreting endocrine system cause organ dysfunction and disease states. However, the cell biology of endocrine tissue ageing remains poorly understood. Here, we perform comparative 3D imaging to understand age‐related perturbations of the endothelial cell (EC) compartment in endocrine glands. Datasets of a wide range of markers highlight a decline in capillary and artery numbers, but not of perivascular cells in pancreas, testis and thyroid gland, with age in mice and humans. Further, angiogenesis and β‐cell expansion in the pancreas are coupled by a distinct age‐dependent subset of ECs. While this EC subpopulation supports pancreatic β cells, it declines during ageing concomitant with increased expression of the gap junction protein Gja1. EC‐specific ablation of Gja1 restores β‐cell expansion in the aged pancreas. These results provide a proof of concept for understanding age‐related vascular changes and imply that therapeutic targeting of blood vessels may restore aged endocrine tissue function. This comprehensive data atlas offers over > 1,000 multicolour volumes for exploration and research in endocrinology, ageing, matrix and vascular biology.

中文翻译:


内分泌系统衰老过程中血管密度和内皮细胞亚群动态降低



与年龄相关的激素分泌内分泌系统的变化会导致器官功能障碍和疾病状态。然而,内分泌组织衰老的细胞生物学仍然知之甚少。在这里,我们进行比较 3D 成像,以了解内分泌腺内皮细胞 (EC) 区室与年龄相关的扰动。各种标记物的数据集强调,随着小鼠和人类年龄的增长,毛细血管和动脉数量减少,但胰腺、睾丸和甲状腺的血管周围细胞却没有减少。此外,胰腺中的血管生成和 β 细胞扩张是由一个独特的年龄依赖性 EC 子集耦合的。虽然该 EC 亚群支持胰腺 β 细胞,但随着衰老过程中,其数量会随着间隙连接蛋白 Gja1 表达的增加而下降。 EC 特异性去除 Gja1 可恢复衰老胰腺中 β 细胞的扩张。这些结果为理解与年龄相关的血管变化提供了概念证明,并意味着针对血管的治疗可以恢复衰老的内分泌组织功能。该综合数据图集提供了超过 > 1,000 个多色卷,用于内分泌学、衰老、基质和血管生物学的探索和研究。
更新日期:2021-01-04
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