LRG1 promotes angiogenesis through upregulating the TGF-β1 pathway in ischemic rat brain

Meng, Hongmei; Song, Yuejia; Zhu, Jiyuan; Liu, Qi; Lu, Pengtian; Ye, Na; Zhang, Zhen; Pang, Yuxin; Qi, Jiping; He, Wei

doi:10.3892/mmr.2016.5925

Cited by 52 publications

(44 citation statements)

References 42 publications

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“…LRG1 has been identified to be positive in endothelial cells owing to its mitogenic activities, thus resulting in the improvement of angiogenesis 10 . Moreover, a previous study demonstrated that, in rats with middle cerebral artery occlusion, LRG1 could promote angiogenesis via the upregulation of the transforming growth factor-β (TGF-β) signaling pathway 11 . Another study also concluded that the migratory machinery of cells was associated with LRG1, because their activities were altered as observed in their performance within the non-canonical TGF-β signaling pathway 12 .…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: MicroRNA-494 Inhibits the LRG1 Expression to Induce Proliferation and Migration of VECs in Rats following Myocardial Infarction

Sun

et al. 2019

Molecular Therapy - Nucleic Acids

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Myocardial infarction (MI) is a life-threatening cardiac event that results in extreme damage to the heart muscle. The Wnt signaling pathway has been implicated in the development of heart diseases. Hence, the current study aimed to investigate the role of microRNA (miRNA) in association with the Wnt signaling pathway to identify potential candidates for MI therapy. Differentially expressed miRNAs associated with MI occurrence were screened, and miR-494 was selected for subsequent experiments. Sprague-Dawley rats were included to establish a MI model via intraperitoneal injection of 0.1 mg/kg atropine sulfate and 40 mg/kg pentobarbital sodium. Then, the interaction between miR-494 and LRG1 was identified. The effect of miR-494 on expression of the Wnt signaling pathway-related genes, proliferation, migration, and invasion ability of fibroblasts and vascular endothelial cells (VECs) was subsequently evaluated through a series of gain- and loss-of-function experiments. The results revealed that miR-494 was poorly expressed and LRG1 was highly expressed in MI rats. miR-494 targets and downregulates LRG1, which resulted in the inactivation of the Wnt signaling pathway and promoted proliferation, migration, and invasion ability of fibroblasts and VECs. In conclusion, this study provided evidence suggesting that overexpressed miR-494 could potentially promote the proliferation, migration, and invasion of fibroblasts and VECs in MI through the inactivation of the Wnt signaling pathway by binding to LRG1.

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Section: Introductionmentioning

confidence: 99%

RETRACTED: MicroRNA-494 Inhibits the LRG1 Expression to Induce Proliferation and Migration of VECs in Rats following Myocardial Infarction

Sun

et al. 2019

Molecular Therapy - Nucleic Acids

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“…Of note, increased levels of TGF‐β were reported in the plasma of stroke patients (Yan, Greer, & McCombe, ) and its expression was induced in the murine brain following ischemia (Zhang et al, ). TGF‐β has been implicated in processes of post‐stroke recovery, including glial scaring and angiogenesis (Meng et al, ; Pardali, Goumans, & ten Dijke, ; Zhu et al, ). In line with these findings, we detected increased levels of TGF‐β1 in the ipsilateral hemispheres of the WT brains 3 days after MCAo (Figure a).…”

Section: Resultsmentioning

confidence: 99%

SorCS2 facilitates release of endostatin from astrocytes and controls post‐stroke angiogenesis

Malik

Lips

Gorniak‐Walas

et al. 2020

Glia

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SorCS2 is an intracellular sorting receptor of the VPS10P domain receptor gene family recently implicated in oxidative stress response. Here, we interrogated the relevance of stress‐related activities of SorCS2 in the brain by exploring its role in ischemic stroke in mouse models and in patients. Although primarily seen in neurons in the healthy brain, expression of SorCS2 was massively induced in astrocytes surrounding the ischemic core in mice following stroke. Post‐stroke induction was likely a result of increased levels of transforming growth factor β1 in damaged brain tissue, inducing Sorcs2 gene transcription in astrocytes but not neurons. Induced astrocytic expression of SorCS2 was also seen in stroke patients, substantiating the clinical relevance of this observation. In astrocytes in vitro and in the mouse brain in vivo, SorCS2 specifically controlled release of endostatin, a factor linked to post‐stroke angiogenesis. The ability of astrocytes to release endostatin acutely after stroke was lost in mice deficient for SorCS2, resulting in a blunted endostatin response which coincided with impaired vascularization of the ischemic brain. Our findings identified activated astrocytes as a source for endostatin in modulation of post‐stroke angiogenesis, and the importance of the sorting receptor SorCS2 in this brain stress response.

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“…lncRNA NONMMUT058334 expression correlated negatively with that of Orly, Dux, Speer4d , and Tango6 , and lncRNA NONMMUT000708 expression correlated positively with that of Hif3a . The mRNAs in the co-expression network were involved in inflammation, neuronal apoptosis, and metabolic pathways [ 33 – 35 ]. Our findings suggest that these differentially expressed lncRNAs participate in POCD by interacting with their corresponding coding genes.…”

Section: Discussionmentioning

confidence: 99%

Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction

et al. 2017

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Postoperative cognitive dysfunction (POCD) is a common postoperative complication observed in elderly patients. Using microarray analyses, we comprehensively compared long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) expression profiles in hippocampal tissues from a mouse model of POCD and control mice. A total of 175 lncRNAs, 117 mRNAs, and 26 miRNAs were differentially expressed between POCD and control mice. Gene ontology (GO) and KEGG pathway enrichment analyses were performed to explore the principal functions of dysregulated genes. Correlated coding-noncoding co-expression (CNC) and competing endogenous RNA (ceRNA) expression networks were constructed using bioinformatics methods. lncRNA NONMMUT000708 correlated positively with expression of the inflammation-related gene Hif3a. lncRNAs NONMMUT043249 and NONMMUT028705 mediated gene expression by binding the transcription factor cAMP response element-binding protein (CREB). The constructed ceRNA network suggested lncRNA NONMMUT055714 binds competitively with miR-7684-5p, increasing expression of its target gene, Sorl1. Finally, eight dysregulated lncRNAs, four miRNAs, and ten mRNAs were confirmed via quantitative real-time polymerase chain reaction (PCR) in 10 POCD-healthy mouse paired samples. These results suggest that lncRNAs and miRNAs are involved in POCD pathogenesis and progression. Our ceRNA network will improve understanding of lncRNA-mediated ceRNA regulatory mechanisms operating during the pathogenesis of POCD.

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LRG1 promotes angiogenesis through upregulating the TGF-β1 pathway in ischemic rat brain

Cited by 52 publications

References 42 publications

RETRACTED: MicroRNA-494 Inhibits the LRG1 Expression to Induce Proliferation and Migration of VECs in Rats following Myocardial Infarction

RETRACTED: MicroRNA-494 Inhibits the LRG1 Expression to Induce Proliferation and Migration of VECs in Rats following Myocardial Infarction

SorCS2 facilitates release of endostatin from astrocytes and controls post‐stroke angiogenesis

Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction

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