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Telocytes in the human ascending aorta: Characterization and exosome-related KLF-4/VEGF-A expression
Journal of Cellular and Molecular Medicine ( IF 5.3 ) Pub Date : 2021-09-25 , DOI: 10.1111/jcmm.16919
Thomas Aschacher 1 , Katy Schmidt 2 , Olivia Aschacher 3 , Eva Eichmair 4 , Ulrike Baranyi 4 , Bernhard Winkler 1 , Martin Grabenwoeger 1 , Andreas Spittler 5 , Florian Enzmann 6 , Barbara Messner 4 , Julia Riebandt 4 , Guenther Laufer 4 , Michael Bergmann 5 , Marek Ehrlich 4
Affiliation  

Telocytes (TCs), a novel interstitial cell entity promoting tissue regeneration, have been described in various tissues. Their role in inter-cellular signalling and tissue remodelling has been reported in almost all human tissues. This study hypothesizes that TC also contributes to tissue remodelling and regeneration of the human thoracic aorta (HTA). The understanding of tissue homeostasis and regenerative potential of the HTA is of high clinical interest as it plays a crucial role in pathogenesis from aortic dilatation to lethal dissection. Therefore, we obtained twenty-five aortic specimens of heart donors during transplantation. The presence of TCs was detected in different layers of aortic tissue and characterized by immunofluorescence and transmission electron microscopy. Further, we cultivated and isolated TCs in highly differentiated form identified by positive staining for CD34 and c-kit. Aortic-derived TC was characterized by the expression of PDGFR-α, PDGFR-β, CD29/integrin β-1 and αSMA and the stem cell markers Nanog and KLF-4. Moreover, TC exosomes were isolated and characterized for soluble angiogenic factors by Western blot. CD34+/c-kit+ TCs shed exosomes containing the soluble factors VEGF-A, KLF-4 and PDGF-A. In summary, TC occurs in the aortic wall. Correspondingly, exosomes, derived from aortic TCs, contain vasculogenesis-relevant proteins. Understanding the regulation of TC-mediated aortic remodelling may be a crucial step towards designing strategies to promote aortic repair and prevent adverse remodelling.

中文翻译:

人类升主动脉中的 Telocytes:表征和外泌体相关的 KLF-4/VEGF-A 表达

Telocyte (TCs) 是一种促进组织再生的新型间质细胞实体,已在各种组织中进行了描述。几乎所有人体组织都报道了它们在细胞间信号传导和组织重塑中的作用。本研究假设 TC 还有助于人胸主动脉 (HTA) 的组织重塑和再生。了解 HTA 的组织稳态和再生潜力具有很高的临床意义,因为它在从主动脉扩张到致死性夹层的发病机制中起着至关重要的作用。因此,我们在移植过程中获得了 25 份心脏供体的主动脉标本。在主动脉组织的不同层中检测到 TC 的存在,并通过免疫荧光和透射电子显微镜进行表征。进一步,我们培养和分离了高度分化形式的 TC,通过 CD34 和 c-kit 的阳性染色鉴定。主动脉来源的 TC 的特征在于 PDGFR-α、PDGFR-β、CD29/整合素 β-1 和 αSMA 以及干细胞标志物 Nanog 和 KLF-4 的表达。此外,通过蛋白质印迹分离和表征 TC 外泌体的可溶性血管生成因子。CD34+ /c-kit + TCs 脱落含有可溶性因子 VEGF-A、KLF-4 和 PDGF-A 的外泌体。总之,TC发生在主动脉壁。相应地,源自主动脉 TC 的外泌体含有与血管发生相关的蛋白质。了解 TC 介导的主动脉重塑的调节可能是设计促进主动脉修复和预防不良重塑策略的关键一步。
更新日期:2021-10-12
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