NF-?B in epiretinal membranes after human diabetic retinopathy

Mitamura, Yoshinori; Harada, Taiki; Harada, Chikako; Ohtsuka, Kenji; Kotake, Satoshi; Ohno, Suguru; Tanaka, Kimihiro; Takeuchi, Shinobu; Wada, Keiji

doi:10.1007/s00125-003-1201-x

Cited by 5 publications

(5 citation statements)

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“…NF‐κB is a transcription factor controlling the expression of many genes including pro‐inflammatory factors, which is a highly inducible factor regulated by MAPKs and confers oxidative properties (Morgan & Liu, 2010; Wang et al, 2018). Proinflammatory cytokines such as TNF‐α and IL‐1β have been demonstrated to induce the expression of ICAM‐1 and VEGF via NF‐κB activation (Harada et al, 2004; Mitamura et al, 2003). In the present study, we observed the activation of NF‐κB in DR as well as the upregulation of its downstream targets, such as TNF‐α, IL‐1β, ICAM‐1, and VEGF.…”

Section: Discussionmentioning

confidence: 99%

Melatonin maintains inner blood‐retinal barrier via inhibition of p38/TXNIP/NF‐κB pathway in diabetic retinopathy

Tang

Zhang

Yang

et al. 2021

Journal Cellular Physiology

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The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti‐inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood–retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF‐α, IL‐1β, ICAM‐1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO‐1, occludin, JAM‐A, and claudin‐5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF‐κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF‐κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin‐based DR therapy.

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Section: Discussionmentioning

confidence: 99%

Melatonin maintains inner blood‐retinal barrier via inhibition of p38/TXNIP/NF‐κB pathway in diabetic retinopathy

Tang

Zhang

Yang

et al. 2021

Journal Cellular Physiology

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“…NF-κB transcription factor family regulates a large amount of genes involved in cell function and inflammation. NF-κB family proteins have been detected in diabetic retinopathy and participate in ganglion cell death, formation of epiretinal membranes, and angiogenesis [27][28][29]. Furthermore, TFAM was found to be involved in the protective role of astrocytes in protecting neurons through NF-κB signaling pathway, indicating the regulatory role of TFAM on NF-κB [30].…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial transcription factor A protects human retinal endothelial cell injury induced by hypoxia

Xie¹,

Cao²

2017

Trop. J. Pharm Res

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Purpose: To investigate the impact of mitochondrial transcription factor A (TFAM), as a modulator of NF-κB, on proliferation of hypoxia-induced human retinal endothelial cell (HREC), and the probable mechanism. Methods: After exposure to hypoxia (1 % O2) for 5 days, cell proliferation and cell cycle of HREC were measured by MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay and flow cytometry. Cell signaling and mitochondrial DNA (mtDNA) copies were determined using real-time polymerase chain reaction and Western blot. NF-κB activity was evaluated by luciferase assay. Results: TFAM expression decreased to 40 % in HREC under hypoxic condition (p < 0.05). MTT results revealed that TFAM facilitated HREC proliferation under hypoxia (p < 0.05). Moreover, flow cytometry demonstrated that TFAM promoted HREC proliferation by accelerating cell cycle (p < 0.05). Western blot and luciferase assay exhibited NF-κB activation in HREC after TFAM overexpression (p < 0.05). Finally, real-time PCR results showed that mtDNA and targeted genes of NF-κB were upregulated 3-fold in HREC after TFAM transfection under hypoxia (p < 0.05). Conclusion: These results indicate that NF-κB activated by TFAM protects against hypoxia-induced HREC injury by accelerating cell cycle. The ability of TFAM to enhance NF-κB signaling may be part of the mechanism of hypoxia-induced cell injury. Thus, upregulation of TFAM may help to relieve diabetic retinopathy.

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“…Studies have reported nuclear NF-k B immunoreactivity (activated state) in the pericytes but not ECs of human diabetic eyes [ 156 ] . In experimental diabetes, however, NF-k B activity is evident in retinal vessel ECs [ 130,[157][158][159] . Furthermore, cultured ECs show increased NF-k B activity and downstream effects when exposed to high levels of glucose [ 63,128,130,137,139,160 ] .…”

Section: Transcription Factorsmentioning

confidence: 99%