Expression of High-Mobility Group Box 1 Protein (HMGB1) and Toll-Like Receptor 9 (TLR9) in Retinas of Diabetic Rats

High-mobility group box 1 (HMGB1) is a protein that is part of a larger family of non-histone nuclear proteins. HMGB1 is a ubiquitary protein with different isoforms, linked to numerous physiological and pathological pathways. HMGB1 is involved in cytokine and chemokine release, leukocyte activation and migration, tumorigenesis, neoangiogenesis, and the activation of several inflammatory pathways. HMGB1 is, in fact, responsible for the trigger, among others, of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), toll-like receptor-4 (TLR-4), and vascular endothelial growth factor (VEGF) pathways. Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM) that is rapidly growing in number. DR is an inflammatory disease caused by hyperglycemia, which determines the accumulation of oxidative stress and cell damage, which ultimately leads to hypoxia and neovascularization. Recent evidence has shown that hyperglycemia is responsible for the hyperexpression of HMGB1. This protein activates numerous pathways that cause the development of DR, and HMGB1 levels are constantly increased in diabetic retinas in both proliferative and non-proliferative stages of the disease. Several molecules, such as glycyrrhizin (GA), have proven effective in reducing diabetic damage to the retina through the inhibition of HMGB1. The main focus of this review is the growing amount of evidence linking HMGB1 and DR as well as the new therapeutic strategies involving this protein.

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“…It may exert its function via the TLR-9 pathway. The expression of TLR-9 was increased and positively related to the expression of HMGB1 [75].…”

Section: Hmgb1 and Drmentioning

confidence: 91%

The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies

et al. 2020

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“…TLR9 is a cytosolic receptor bound to the membranes of intracellular organelles (e.g., endosomes, lysosomes, and endolysosomes) and is responsible for identification of unmethylated cytosine-phosphate-guanosine DNA present in bacteria and viruses [ 211 , 254 , 255 ]. Furthermore, TLR9 has been shown to directly contribute to cardiac, hepatic, and renal ischemic tissue injury [ 211 ] and lupus nephritis [ 256 , 257 ] through recognition of endogenous mitochondrial DNA products [ 258 ], chromatin IgG complex [ 259 ], GP96 [ 260 ], high-mobility group box-1 [ 261 ], and heat-shock protein 90 [ 262 ]. A study involving CIAKI determined a protective immunomodulating role of TLR9 in disease progression, as TLR9 absence resulted in accelerated and increased pathological development [ 56 ].…”

Section: Cisplatin-induced Acute Kidney Injury: Role Of the Immunementioning

confidence: 99%

Mechanisms of Cisplatin-Induced Acute Kidney Injury: Pathological Mechanisms, Pharmacological Interventions, and Genetic Mitigations

McSweeney

Gadanec

Qaradakhi

et al. 2021

Cancers

185

134

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Administration of the chemotherapeutic agent cisplatin leads to acute kidney injury (AKI). Cisplatin-induced AKI (CIAKI) has a complex pathophysiological map, which has been linked to cellular uptake and efflux, apoptosis, vascular injury, oxidative and endoplasmic reticulum stress, and inflammation. Despite research efforts, pharmaceutical interventions, and clinical trials spanning over several decades, a consistent and stable pharmacological treatment option to reduce AKI in patients receiving cisplatin remains unavailable. This has been predominately linked to the incomplete understanding of CIAKI pathophysiology and molecular mechanisms involved. Herein, we detail the extensively known pathophysiology of cisplatin-induced nephrotoxicity that manifests and the variety of pharmacological and genetic alteration studies that target them.

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“…Levels of HMGB1 are increased in retinas of diabetic rats [123,124] and in patients with proliferative diabetic retinopathy (PDR) [125,126], together with endothelial activity biomarkers like ICAM-1, sICAM-1, MCP-1, VEGF, Granulocyte-colony stimulating factor (G -CSF), sVE-cadherin and soluble endoglin (sEng), supporting the contribution of HMGB1 in neovascularization process [123,[125][126][127][128][129]. Moreover, El-Asrar and coworkers demonstrated that levels of HMGB1 are higher in patients with PDR and retinal hemorrhages, suggesting a role of the protein in PDR progression [126].…”

Section: Hmgb1 and Diabetic Retinopathymentioning

confidence: 99%

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

Biscetti

Rando

Nardella

et al. 2019

IJMS

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Diabetes mellitus (DM) is an endemic disease, with growing health and social costs. The complications of diabetes can affect potentially all parts of the human body, from the heart to the kidneys, peripheral and central nervous system, and the vascular bed. Although many mechanisms have been studied, not all players responsible for these complications have been defined yet. High Mobility Group Box-1 (HMGB1) is a non-histone nuclear protein that has been implicated in many pathological processes, from sepsis to ischemia. The purpose of this review is to take stock of all the most recent data available on the role of HMGB1 in the complications of DM.

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Expression of High-Mobility Group Box 1 Protein (HMGB1) and Toll-Like Receptor 9 (TLR9) in Retinas of Diabetic Rats

Cited by 14 publications

References 21 publications

The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies

The Complex Relationship between Diabetic Retinopathy and High-Mobility Group Box: A Review of Molecular Pathways and Therapeutic Strategies

Mechanisms of Cisplatin-Induced Acute Kidney Injury: Pathological Mechanisms, Pharmacological Interventions, and Genetic Mitigations

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

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