Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors

Lazzara, Francesca; Trotta, Maria Consiglia; Platania, Chiara Bianca Maria; D’Amico, Michele; Petrillo, Francesco; Galdiero, Marilena; Gesualdo, Carlo; Rossi, Silvia; Drago, Filippo; Bucolo, Claudio

doi:10.3389/fphar.2020.01063

Cited by 45 publications

(28 citation statements)

References 72 publications

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“…Altogether, these experimental observations would suggest that in RPE cells exposed to HG stress induction of autophagy represents a cytoprotective response. Accordingly, treatment with fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist by preventing ER-stress and inducing autophagy, exhibited a protective effect in RPE cells exposed to hyperglycemia (25 mM, 18 days) and hypoxia (1% oxygen, for 6 h or 24 h), two components of the diabetic milieu (Miranda et al, 2012;Lazzara et al, 2020).…”

Section: Retinal Pigment Epithelial Cellsmentioning

confidence: 99%

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

et al. 2021

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Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology. Here we review the role of autophagy in experimental models of DR and explore the potential of this pathway as a target for alternative therapeutic approaches.

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Section: Retinal Pigment Epithelial Cellsmentioning

confidence: 99%

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

et al. 2021

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“…Zhang et al [ 30 ] interfered HIF-1α with small molecular RNA in mice, and found that silencing of HIF-1α could reduce VEGF expression and inhibit angiogenesis. In chemical (CoCl 2 ) hypoxia-induced hRECs, the expression of HIF-1α and VEGF was increased and activation of HIF-1α could upregulate the expression of VEGF [ 31 ]. HG-induced increased expression of VEGF, leading to the induction of apoptosis of hRECs via binding to VEGFR2 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Celastrol inhibits the proliferation and angiogenesis of high glucose-induced human retinal endothelial cells

Fang¹,

Chang

2021

BioMed Eng OnLine

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Background Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes. Celastrol plays a certain role in the improvement of various diabetes complications. Therefore, this study aimed to explore whether celastrol inhibited the proliferation and angiogenesis of high glucose (HG)-induced human retinal endothelial cells (hRECs) by down-regulating the HIF1/VEGF signaling pathway. Methods The viability and proliferation of hRECs treated with glucose, celastrol or dimethyloxallyl glycine (DMOG) were analyzed by MTT assay. The invasion and tube formation ability of hRECs treated with glucose, celastrol or DMOG were in turn detected by transwell assay and tube formation assay. The expression of HIF1α and VEGF in hRECs after indicated treatment was analyzed by Western blot analysis and RT-qPCR analysis and ICAM-1 expression in hRECs after indicated treatment was detected by immunofluorescence assay Results HG induction promoted the proliferation, invasion and tube formation ability and increased the expression of HIF-1α and VEGF of hRECs, which were gradually suppressed by celastrol changing from 0.5 to 2.0 μM. DMOG was regarded as a HIF1α agonist, which attenuated the effect of celastrol on HG-induced hRECs. Conclusion Celastrol inhibited the proliferation and angiogenesis of HG-induced hRECs by down-regulating the HIF1α/VEGF signaling pathway.

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“…EPO treatment can effectively protect the nervous system and optic nerve development of premature infants[ 42 , 43 ]. HIF-1α is stably expressed under hypoxia; it can regulate EPO and VEGF expression and promote RNV[ 44 , 45 ]. Inhibiting the VEGF/VEGFR2 and HIF-1α/VEGF signaling pathways can prevent angiogenesis[ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

Yu¹,

Ren²,

Chen³

2021

WJD

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BACKGROUND As one of the major microvascular complications of diabetes, diabetic retinopathy (DR) is the leading cause of blindness in the working age population. Because the extremely complex pathogenesis of DR has not been fully clarified, the occurrence and development of DR is closely related to tissue ischemia and hypoxia and neovascularization The formation of retinal neovascularization (RNV) has great harm to the visual acuity of patients. AIM To investigate the expression of P-element-induced wimpy testis-interacting RNA (piRNA) in proliferative DR mice and select piRNA related to RNV. METHODS One hundred healthy C57BL/6J mice were randomly divided into a normal group as control group (CG) and proliferative DR (PDR) group as experimental group (EG), with 50 mice in each group. Samples were collected from both groups at the same time, and the lesions of mice were evaluated by hematoxylin and eosin staining and retinal blood vessel staining. The retinal tissues were collected for second-generation high-throughput sequencing, and the differentially expressed piRNA between the CG and EG was detected, and polymerase chain reaction (PCR) was conducted for verification. The differentially obtained piRNA target genes and expression profiles were enrichment analysis based on gene annotation (Gene Ontology) and Kyoto Encyclopedia of Genes and Genomes. RESULTS In the CG there was no perfusion area, neovascularization and endothelial nucleus broke through the inner boundary membrane of retinap. In the EG, there were a lot of nonperfused areas, new blood vessels and endothelial nuclei breaking through the inner boundary membrane of the retina. There was a statistically significant difference in the number of vascular endothelial nuclei breaking through the inner retinal membrane between the two groups. High-throughput sequencing analysis showed that compared with the CG, a total of 79 piRNAs were differentially expressed in EG, among which 43 piRNAs were up-regulated and 36 piRNAs were down-regulated. Bioinformatics analysis showed that the differentially expressed piRNAs were mainly concentrated in the signaling pathways of angiogenesis and cell proliferation. Ten piRNAs were selected for PCR, and the results showed that the expression of piR-MMU-40373735, piR-MMU-61121420, piR-MMU-55687822, piR-MMU-1373887 were high, and the expression of piR-MMU-7401535, piR-MMU-4773779, piR-MMU-1304999, and piR-MMU-5160126 were low, which were consistent with the sequencing results. CONCLUSION In the EG, the abnormal expression of piRNA is involved in the pathway of angiogenesis and cell proliferation, suggesting that piRNAs have some regulatory function in proliferative diabetic-retinopathy.

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Stabilization of HIF-1α in Human Retinal Endothelial Cells Modulates Expression of miRNAs and Proangiogenic Growth Factors

Cited by 45 publications

References 72 publications

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy

Celastrol inhibits the proliferation and angiogenesis of high glucose-induced human retinal endothelial cells

Expression and role of P-element-induced wimpy testis-interacting RNA in diabetic-retinopathy in mice

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