miR‐370 inhibits the angiogenic activity of endothelial cells by targeting smoothened (SMO) and bone morphogenetic protein (BMP)‐2

Gu, Yuan; Becker, Vivien; Zhao, Yingjun; Menger, Michael D.; Laschke, Matthias W.

doi:10.1096/fj.201802085rr

Cited by 16 publications

(17 citation statements)

References 36 publications

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“…Besides these, many tissue types exist in the bone, including vascular endothelium and connective tissues and autonomic and sensory nerves, which contribute to forming a favorable milieu for bone formation 48,49 . BMPs belong to the TGF-β super-family, which are recognized as playing critical roles in regulating bone formation and proliferation 50,51 , as well as in angiogenesis 52,53 . However, some members of BMPs can commit MSCs to osteoblast lineages, such BMP2, BMP4, BMP6, and BMP7 54,55 .…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

Liu

Tang

et al. 2020

Cell Death Dis

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Human amniotic mesenchymal stem cells (hAMSCs) are multiple potent progenitor cells (MPCs) that can differentiate into different lineages (osteogenic, chondrogenic, and adipogenic cells) and have a favorable capacity for angiogenesis. Schnurri-3 (Shn3) is a large zinc finger protein related to Drosophila Shn, which is a critical mediator of postnatal bone formation. Bone morphogenetic protein 9 (BMP9), one of the most potent osteogenic BMPs, can strongly upregulate various osteogenesis-and angiogenesis-related factors in MSCs. It remains unclear how Shn3 is involved in BMP9-induced osteogenic differentiation coupled with angiogenesis in hAMSCs. In this investigation, we conducted a comprehensive study to identify the effect of Shn3 on BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs and analyze the responsible signaling pathway. The results from in vitro and in vivo experimentation show that Shn3 notably inhibits BMP9-induced early and late osteogenic differentiation of hAMSCs, expression of osteogenesis-related factors, and subcutaneous ectopic bone formation from hAMSCs in nude mice. Shn3 also inhibited BMP9-induced angiogenic differentiation, expression of angiogenesis-related factors, and subcutaneous vascular invasion in mice. Mechanistically, we found that Shn3 prominently inhibited the expression of BMP9 and activation of the BMP/Smad and BMP/MAPK signaling pathways. In addition, we further found activity on runt-related transcription factor 2 (Runx2), vascular endothelial growth factor (VEGF), and the target genes shared by BMP and Shn3 signaling pathways. Silencing Shn3 could dramatically enhance the expression of Runx2, which directly regulates the downstream target VEGF to couple osteogenic differentiation with angiogenesis. To summarize, our findings suggested that Shn3 significantly inhibited the BMP9-induced osteogenic differentiation and angiogenesis in hAMSCs. The effect of Shn3 was primarily seen through inhibition of the BMP/Smad signaling pathway and depressed expression of Runx2, which directly regulates VEGF, which couples BMP9-induced osteogenic differentiation with angiogenesis.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

Liu

Tang

et al. 2020

Cell Death Dis

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“…Therefore, by regulating VEGF-dependent angiogenesis, miRNA-370 and miRNA-10a may potentially impact the pathophysiology of HHT1 and HHT2. Of note, several experimental reports have already demonstrated the involvement of miRNA-370 in different functions of endothelial cells, the target cells in HHT where endoglin is predominantly expressed [38,40]. Thus, miRNA-370 suppresses retinal capillary endothelial cell growth and apoptosis [38], inhibits the angiogenic activity of endothelial cells, and reduces microvessel density and sprouting in vivo, whereas a miRNA-370 inhibitor promotes endothelial sprout formation [40].…”

Section: Discussionmentioning

confidence: 99%

“…Of note, several experimental reports have already demonstrated the involvement of miRNA-370 in different functions of endothelial cells, the target cells in HHT where endoglin is predominantly expressed [38,40]. Thus, miRNA-370 suppresses retinal capillary endothelial cell growth and apoptosis [38], inhibits the angiogenic activity of endothelial cells, and reduces microvessel density and sprouting in vivo, whereas a miRNA-370 inhibitor promotes endothelial sprout formation [40]. The antiangiogenic activity of miRNA-370 is fully compatible with the key functional role of its putative target endoglin in endothelial cells, as endoglin promotes angiogenesis in vivo and in vitro, at least, by stimulating proliferation and anti-apoptotic activity of endothelial cells [61].…”

Section: Discussionmentioning

confidence: 99%

“…miRNA-370 can also induce growth and tube formation inhibition, and apoptosis in endothelial cells [37,38]. The miRNA-370-induced endothelial effects may explain its anti-angiogenic activity, as well as its developmental regulation of cerebral aneurysms [38][39][40]. Noteworthy, the effects miRNA-370 are mediated by targeting, at least, a receptor for vascular endothelial growth factor (VEGF), which is the major driver of angiogenesis [38,39].…”

Section: Identification Of Mirna-10a Mirna-214 and Mirna-370 Potenmentioning

confidence: 99%

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Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia

Ruíz-Llorente

Albiñana

Botella

et al. 2020

JCM

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Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant, vascular disorder that presents with telangiectases and arteriovenous malformations. HHT is a genetically heterogeneous disorder, involving mutations in endoglin (ENG; HHT1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT2) genes that account for over 85% of all HHT patients. The current diagnosis of HHT patients remains at the clinical level, but many suspected patients do not have a clear HHT diagnosis or do not show pathogenic mutations in HHT genes. This situation has prompted the search for biomarkers to help in the early diagnosis of the disease. We have analyzed the plasma levels in HHT patients of selected micro-RNAs (miRNAs), small single-stranded RNAs that regulate gene expression at the transcriptional level by interacting with specific RNA targets. A total of 16 HHT1 and 17 HHT2 plasma samples from clinically confirmed patients and 16 controls were analyzed in this study. Total RNA was purified from plasma, and three selected miRNAs (miRNA-10a, miRNA-214, and miRNA-370), related to the pathobiology of cardiovascular diseases and potentially targeting ENG or ALK1, were measured by quantitative polymerase chain reaction. Compared with controls, levels of miRNA-370, whose putative target is ENG, were significantly downregulated in HHT1, but not in HHT2, whereas the levels of miRNA-10a, whose putative target is ALK1, were significantly upregulated in HHT2, but not in HHT1. In addition, the levels of miRNA-214, potentially targeting ENG and ALK1, did not change in either HHT1 or HHT2 patients versus control samples. While further studies are warranted, these results suggest that dysregulated plasma levels of miRNA-370 or miRNA-10a could help to identify undiagnosed HHT1 or HHT2 patients, respectively.

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“…MiR-370 has been experimentally validated to target ENG in ovarian cancer cells [ 75 ], yet its role in EC function and angiogenesis is unclear, as multiple reports have demonstrated conflicting evidence. Overexpression of miR-370 inhibited proliferation, migration and tube formation in human dermal microvascular ECs, retinal capillary ECs and HUVECs [ 76 , 77 ]. In contrast, miR-370 overexpression was shown to promote HUVEC proliferation, migration and tube formation to facilitate healing after finger amputation [ 78 ].…”

Section: Circulating Mir Biomarkers In Hhtmentioning

confidence: 99%

Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia

Cannavicci

Zhang

Kutryk

2020

JCM

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Non-coding RNAs (ncRNAs) are functional ribonucleic acid (RNA) species that include microRNAs (miRs), a class of short non-coding RNAs (∼21–25 nucleotides), and long non-coding RNAs (lncRNAs) consisting of more than 200 nucleotides. They regulate gene expression post-transcriptionally and are involved in a wide range of pathophysiological processes. Hereditary hemorrhagic telangiectasia (HHT) is a rare disorder inherited in an autosomal dominant fashion characterized by vascular dysplasia. Patients can develop life-threatening vascular malformations and experience severe hemorrhaging. Effective pharmacological therapies are limited. The study of ncRNAs in HHT is an emerging field with great promise. This review will explore the current literature on the involvement of ncRNAs in HHT as diagnostic and pathogenic factors.

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miR‐370 inhibits the angiogenic activity of endothelial cells by targeting smoothened (SMO) and bone morphogenetic protein (BMP)‐2

Cited by 16 publications

References 36 publications

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

RETRACTED ARTICLE: Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF

Differential Expression of Circulating Plasma miRNA-370 and miRNA-10a from Patients with Hereditary Hemorrhagic Telangiectasia

Non-Coding RNAs and Hereditary Hemorrhagic Telangiectasia

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