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细胞外核苷酸影响成纤维细胞、角质形成细胞和内皮细胞的促血管生成行为。

Extracellular Nucleotides Affect the Proangiogenic Behavior of Fibroblasts, Keratinocytes, and Endothelial Cells.

机构信息

Institute of Molecular and Industrial Biotechnology, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 2/22, 90-537 Lodz, Poland.

Department of Experimental Surgery, Medical University of Lodz, 93-513 Lodz, Poland.

出版信息

Int J Mol Sci. 2021 Dec 27;23(1):238. doi: 10.3390/ijms23010238.

DOI:10.3390/ijms23010238
PMID:35008664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8745609/
Abstract

Chronic wound healing is currently a severe problem due to its incidence and associated complications. Intensive research is underway on substances that retain their biological activity in the wound microenvironment and stimulate the formation of new blood vessels critical for tissue regeneration. This group includes synthetic compounds with proangiogenic activity. Previously, we identified phosphorothioate analogs of nucleoside 5'-O-monophosphates as multifunctional ligands of and receptors. The effects of a series of unmodified and phosphorothioate nucleotide analogs on the secretion of VEGF from keratinocytes and fibroblasts, as well as their influence on the viability and proliferation of keratinocytes, fibroblasts, and endothelial cells were analyzed. In addition, the expression profiles of genes encoding nucleotide receptors in tested cell models were also investigated. In this study, we defined thymidine 5'-O-monophosphorothioate (TMPS) as a positive regulator of angiogenesis. Preliminary analyses confirmed the proangiogenic potency of TMPS in vivo.

摘要

慢性伤口愈合是目前一个严重的问题,因为它的发病率和相关的并发症。目前正在对在伤口微环境中保持生物活性并刺激新血管形成的物质进行深入研究,这些新血管对组织再生至关重要。这组物质包括具有促血管生成活性的合成化合物。以前,我们已经鉴定出核苷 5'-O-单磷酸的硫代磷酸酯类似物是 和 受体的多功能配体。分析了一系列未修饰和硫代磷酸核苷酸类似物对角质形成细胞和成纤维细胞分泌 VEGF 的影响,以及它们对角质形成细胞、成纤维细胞和内皮细胞活力和增殖的影响。此外,还研究了测试细胞模型中编码核苷酸受体的基因的表达谱。在这项研究中,我们将胸苷 5'-O-单磷酸硫代酯 (TMPS) 定义为血管生成的正调节剂。初步分析证实了 TMPS 在体内的促血管生成作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3baa/8745609/0f7f334c0c8d/ijms-23-00238-g006.jpg
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