抑制 BMP4 可通过血管内皮生长因子和 smad1/5 信号缓解糖尿病视网膜血管功能障碍。

IF 2.5 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM Archives of Physiology and Biochemistry Pub Date : 2024-10-01 Epub Date: 2023-04-19 DOI:10.1080/13813455.2023.2190054
Mingyuan Liu, Zhaoxia Li, Huiqin Zhang, Tingting Cao, Xueyan Feng, Xi Wang, Zhixue Wang
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引用次数: 0

摘要

目的:我们的研究旨在确定BMP4(骨形态发生蛋白4)在DR(糖尿病视网膜病变)中的分子机制。方法:通过高糖诱导人视网膜内皮细胞(HRECs)来模拟糖尿病视网膜病变(DR)模型的发病机制之一。采用 RT-qPCR 和 Western 印迹法检测 STZ/HG 组 BMP4 的 mRNA 和蛋白水平。流式细胞术和TUNEL染色检测细胞凋亡。通过血管形成试验评估血管生成。Transwell试验和伤口愈合试验用于检测细胞迁移能力。H&E染色用于评估病理变化:结果:BMP4在STZ/HG组明显上调。Sh-BMP4能明显抑制HG诱导的RVECs迁移和血管生成。此外,体内和体外实验均证实,sh-BMP4 能明显促进 HG/STZ 组 RVECs 的凋亡。Western blot结果显示,sh-BMP4能下调p-smad1、p-smad5和VEGF的表达:结论:抑制BMP4可通过调节p-smad1/5/VEGF信号轴、抑制血管生成和促进细胞凋亡减轻糖尿病视网膜病变的损伤。
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Inhibition of BMP4 alleviates diabetic retinal vascular dysfunction via the VEGF and smad1/5 signalling.

Objective:The aim of our study was to determine the molecular mechanism of BMP4 (bone morphogenetic protein 4) in DR (diabetic retinopathy).Methods: Human retinal endothelial cell (HRECs) induced by high glucose to simulate one of the pathogenesis in the diabetic retinopathy (DR) model. RT-qPCR and western blot were used to detect the mRNA and protein levels of BMP4 in the STZ/HG group. Flow cytometry and TUNEL staining were performed to detect the apoptosis. Angiogenesis was evaluated by tube formation assay. Transwell assay and wound healing assay were used to detect cell migration ability. H&E staining was used to evaluate the pathological changes.Results: BMP4 was significantly upregulated in the STZ/HG group. Sh-BMP4 significantly inhibited the migration and angiogenesis of RVECs induced by HG. In addition, both in vivo and in vitro experiments confirmed that sh-BMP4 could significantly promote RVECs apoptosis in the HG/STZ group. Western blot results showed that sh-BMP4 could down-regulate the expressions of p-smad1, p-smad5 and VEGF.Conclusions: Inhibition of BMP4 could alleviate the damage of diabetic retinopathy by regulating the p-smad1/5/VEGF signaling axis, inhibiting angiogenesis and promoting apoptosis.

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来源期刊
Archives of Physiology and Biochemistry
Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY
CiteScore
6.90
自引率
3.30%
发文量
21
期刊介绍: Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.
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