Mingyuan Liu, Zhaoxia Li, Huiqin Zhang, Tingting Cao, Xueyan Feng, Xi Wang, Zhixue Wang
{"title":"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。","authors":"Mingyuan Liu, Zhaoxia Li, Huiqin Zhang, Tingting Cao, Xueyan Feng, Xi Wang, Zhixue Wang","doi":"10.1080/13813455.2023.2190054","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objective</b>:The aim of our study was to determine the molecular mechanism of BMP4 (bone morphogenetic protein 4) in DR (diabetic retinopathy).<b>Methods</b>: 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.<b>Results</b>: 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.<b>Conclusions</b>: Inhibition of BMP4 could alleviate the damage of diabetic retinopathy by regulating the p-smad1/5/VEGF signaling axis, inhibiting angiogenesis and promoting apoptosis.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"529-536"},"PeriodicalIF":2.5000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Inhibition of BMP4 alleviates diabetic retinal vascular dysfunction via the VEGF and smad1/5 signalling.\",\"authors\":\"Mingyuan Liu, Zhaoxia Li, Huiqin Zhang, Tingting Cao, Xueyan Feng, Xi Wang, Zhixue Wang\",\"doi\":\"10.1080/13813455.2023.2190054\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Objective</b>:The aim of our study was to determine the molecular mechanism of BMP4 (bone morphogenetic protein 4) in DR (diabetic retinopathy).<b>Methods</b>: 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.<b>Results</b>: 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.<b>Conclusions</b>: Inhibition of BMP4 could alleviate the damage of diabetic retinopathy by regulating the p-smad1/5/VEGF signaling axis, inhibiting angiogenesis and promoting apoptosis.</p>\",\"PeriodicalId\":8331,\"journal\":{\"name\":\"Archives of Physiology and Biochemistry\",\"volume\":\" \",\"pages\":\"529-536\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Physiology and Biochemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13813455.2023.2190054\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/4/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Physiology and Biochemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13813455.2023.2190054","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/19 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
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.
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.