Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis

Lam, Jonathan D.; Oh, Daniel J.; Wong, Lindsay L.; Amarnani, Dhanesh; Park‐Windhol, Cindy; Sanchez, Angie V.; Cardona-Vélez, Jonathan; McGuone, Declan; Stemmer‐Rachamimov, Anat; Eliott, Dean; Bielenberg, Diane R.; Zyl, Tavé van; Shen, Lishuang; Gai, Xiaowu; D’Amore, Patricia A.; Kim, Leo A.; Arboleda‐Velásquez, Joseph F.

doi:10.2337/db16-1035

Cited by 62 publications

(80 citation statements)

References 28 publications

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“…Some reports show that the inhibition of RUNX1 activity results in the reduction of neovascular tufts in retinopathy [24], suggesting that RUNX1 has a close relationship with angiogenesis. Hence, we constructed DR model to investigate the expression level of RUNX1 and level of angiogenesis.…”

Section: Runx1 Was Highly Expressed In Diabetic Retinopathymentioning

confidence: 99%

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

et al. 2020

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Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and is characterized by visible microvascular alterations including retinal ischemia–reperfusion injury, inflammation, abnormal permeability, neovascularization and macular edema. Despite the available treatments, some patients present late in the course of the disease when treatment is more difficult. Hence, it is crucial that the new targets are found and utilized in the clinical therapy of DR. In the present study, we constructed a DR animal model and a model in HRMECs to investigate the relationship between p38 and RUNX1 in retinal micro-angiogenesis in diabetic retinopathy. We found that p38 could promote retinal micro-angiogenesis by up-regulating RUNX1 expression in diabetic retinopathy. This suggested that the p38/ RUNX1 pathway could become a new retinal micro-angiogenesis target in DR treatment.

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Section: Runx1 Was Highly Expressed In Diabetic Retinopathymentioning

confidence: 99%

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

et al. 2020

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“…Therefore, the cause of increased vascular permeability in DM remains to be further studied. As an endothelial cell marker, CD31 has been widely used to study aberrant angiogenesis in the eye . Immunohistochemistry (IHC) analysis using anti‐CD31 antibody indicated increases of vascular area in the retina of the DM mice (Figure A).…”

Section: Discussionmentioning

confidence: 66%

“…Neovascularization is a pathological feature of PDR. CD31 has been widely used as an endothelial cell marker to study the aberrant angiogenesis in the eye . Herein, we evaluated angiogenesis using CD31 staining of retinas in DM mice.…”

Section: Resultsmentioning

confidence: 99%

EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

Yang

Yan

et al. 2018

Clin Exp Pharma Physio

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Diabetic retinopathy (DR) is one of the most frequently occurring microvascular complications of diabetes. Recent evidence indicates that epidermal growth factor receptors (EGFRs) are critical pathogenic players in non-neoplastic diseases, including diabetic cardiomyopathy and DR. However, the precise pathogenic mechanism of EGFR in DR has yet to be fully understood. In this study, we developed a type 1 diabetic early-stage retinopathy mouse model using injections of streptozotocin and an oxygen-induced end-stage diabetic retinopathy (OIR) model characterized by hypoxia-induced revascularization. We tested the hypothesis that the pathogenesis of DR can be reduced by the classic EGFR inhibitor, AG1478, in the mouse models. Our data indicated that treatment of AG1478 prevented retinal dysfunction, and reduced impairment of retinal structures as well as mitochondrial structures in retinal blood vessels in diabetic mice. Furthermore, AG1478 reduced neovascular tufts formation but had no effects on revascularization at the avascular sites when compared to untreated littermates in the OIR model. Our findings provide strong evidence that EGFR critically promoted retinal dysfunction, retinal structural impairment, and retinal vascular abnormalities in models of DR. We conclude that EGFR can be a potential important therapeutic target for treatment of DR.

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“…Previous studies have suggested that CAMs are important in the development of DR (Khalfaoui et al, 2009;Ugurlu et al, 2013 of insulin and is associated with DR neovascularization (Qin, Zhang, & Xu, 2015;Sasore, Reynolds, & Kennedy, 2014). Compared with the results of transcriptomic analysis which use CD31+ vascular endothelial cells obtained from human PDR fibrovascular membranes (FVM) (Lam et al, 2017), we found the gene Col3a1 were both significantly changed, and according to the GO enrichment analysis of two researches, Col3a1 may belong to blood vessel development term (GO:0001568), suggested that Col3a1 may play a role in DR neovascularization. We also found that the positive regulation of immune system process term (GO: 0002684) was both significantly enriched in two researches.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel differentially expressed genes in retinas of STZ‐induced long‐term diabetic rats through RNA sequencing

Xing

Jiang

Zhang

et al. 2020

Molec Gen & Gen Med

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Background The aim of this research was to investigate the retinal transcriptome changes in long‐term streptozotocin (STZ)‐induced rats' retinas using RNA sequencing (RNA‐seq), to explore the molecular mechanisms of diabetic retinopathy (DR), and to identify novel targets for the treatment of DR by comparing the gene expression profile we obtained. Methods In this study, 6 healthy male SD rats were randomly divided into wild‐type (WT) group and streptozotocin (STZ)‐induced group, 3 rats each group. After 6 months, 3 normal retina samples and 3 DM retina samples (2 retinas from the same rat were considered as 1 sample) were tested and differentially expressed genes (DEGs) were measured by RNA‐seq technology. Then, we did Gene Ontology (GO) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and validated the results of RNA‐seq through qRT–PCR. Results A total of 118 DEGs were identified, of which 72 were up‐regulated and 46 were down‐regulated. The enriched GO terms showed that 3 most significant enrichment terms were binding (molecular function), cell part (cellular component), and biological regulation (biological process). The results of the KEGG pathway analysis revealed a significant enrichment in cell adhesion molecules, PI3K‐Akt signaling pathway, and allograft rejection, etc. Conclusion Our research has identified specific DEGs and also speculated their potential functions, which will provide novel targets to explore the molecular mechanisms of DR.

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Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis

Cited by 62 publications

References 28 publications

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

p38 promoted retinal micro-angiogenesis through up-regulated RUNX1 expression in diabetic retinopathy

EGFR inhibitor, AG1478, inhibits inflammatory infiltration and angiogenesis in mice with diabetic retinopathy

Identification of novel differentially expressed genes in retinas of STZ‐induced long‐term diabetic rats through RNA sequencing

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