Animal Models and Renal Biomarkers of Diabetic Nephropathy

Pérez-López, Laura; Boronat, Mauro; Melián, Carlos; Brito‐Casillas, Yeray; Wägner, Ana M.

doi:10.1007/5584_2020_527

Cited by 15 publications

(8 citation statements)

References 187 publications

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“…The primary clinical symptom of DN is progressive albuminuria [ 5 , 6 ], but the underlying mechanism still needs to be elucidated. Despite recent advances in DN research, there has been no breakthrough in developing reliable early diagnostic markers or effective treatments for this devastating disease [ 7 – 10 ]. Therefore, there is an unmet medical need to understand the pathogenesis of DN better for facilitating the discovery and development of new targeted therapies.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway

et al. 2023

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Progressive albuminuria is the primary clinical symptom of diabetic nephropathy (DN), leading to a gradual decline in kidney function. DLX6-AS1 was the first reported long non-coding RNA (lncRNA) to participate in organogenesis and play crucial roles in the brain or neural cell development. Herein, we investigated the DLX6-AS1 (Dlx6-os1 in mice) role in DN pathogenesis. We found that DLX6-AS1 expression in DN patients correlated with the extent of albuminuria. Dlx6-os1 overexpression induced cellular damage and inflammatory responses in cultured podocytes through miR-346-mediated regulation of the GSK-3β pathway. In various established diabetic and newly developed knockout mouse models, Dlx6-os1 knockdown/knockout significantly reduced podocyte injury and albuminuria. The Dlx6-os1 effects were remarkably modulated by miR-346 mimics or mutants and significantly diminished in podocyte-specific GSK-3β-knockout mice. Thus, DLX6-AS1 (Dlx6-os1) promotes DN development by accelerating podocyte injury and inflammation through the upregulation of the GSK-3β pathway, providing a novel molecular target for DN therapy.

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Section: Introductionmentioning

confidence: 99%

Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway

et al. 2023

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“…In a recent study, it was also confirmed that ombuin has the potential to improve type 2 diabetes (Kikiowo et al, 2020). Establishing animal models of rodent diabetes by using a high‐fat diet combined with STZ is a common model for human DN research, although this model is not entirely consistent with the pathophysiological characteristics of DN (Pérez‐López et al, 2020). In this study, we demonstrated that ombuin dose‐dependently controlled the RBG levels in diabetic rats induced by a high‐fat diet combined with STZ, and improved 24 h urine volume, UPr, SCr, BUN, kidney index, serum AGE, and renal AGE of diabetic rats.…”

Section: Discussionmentioning

confidence: 99%

Ombuin ameliorates diabetic nephropathy in rats by anti‐inflammation and antifibrosis involving Notch 1 and PPAR γ signaling pathways

Liu

Deng

Tan

2022

Drug Development Research

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Diabetic nephropathy (DN) is a common complication of diabetes and it is urgent to develop effective therapies for DN. In this study, high‐sucrose and high‐fat diet combined with streptozotocin was used to induce DN in rats to observe the effects of natural flavonoid ombuin on renal function, inflammation, and interstitial fibrosis. Immunohistochemistry and western blotting analysis were used to detect protein expression levels. Results showed that ombuin significantly improved renal function and pathological injury, inhibited accumulation of advanced glycation end‐products, suppressed the release of inflammatory cytokines, and improved renal interstitial fibrosis in DN rats. Ombuin also significantly downregulated the expressions of transforming growth factor beta1 (TGF‐β1), connective tissue growth factor (CTGF), fibronectin (FN), p65, phosphorylated (p)‐p65, Cleaved‐Notch 1, and hairy and enhancer of split 1 (Hes 1), and upregulated the expression of peroxisome proliferator‐activated receptor γ (PPAR γ). When PPAR γ activity was inhibited by T0070907, the effects of ombuin on improving DN were significantly reversed, and the expressions of TGF‐β1, FN, CTGF, p‐p65, and p65 increased, while the expressions of Cleaved‐Notch 1 and Hes 1 were not significantly affected. These results suggest that ombuin may activate PPAR γ to exert anti‐inflammatory and antifibrotic effects by inhibiting Notch 1 activity in DN. It is also possible that ombuin acts on these two independent signal pathways synchronously.

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“…The early clinical diagnosis of DN is based on canonical biochemical markers, such as glomerular filtration rate, urinary microalbumin, urinary microalbumin to urinary creatinine ratio, serum creatinine, urinary cystatin C, and serum β 2 microglobulin. In addition, some biomarkers related to the pathogenesis of DN, such as kidney injury molecule 1 (Kim-1), neutrophil gelatinase-associated lipocalin (NGAL), tissue inhibitor of metalloproteinases-2, insulin-like growth factor-binding protein 7 (IGFBP-7), vascular endothelial growth factor (VEGF), transforming growth factor- β (TGF- β ), monocyte chemoattractant protein-1(MCP-1), and inflammatory cytokines, such as tumor necrosis factor (TNF)- α , MCP-1, and ILs (IL-1 α , IL-1 β , IL-18, IL-10), have also attracted significant attention [ 24 , 25 ]. However, the pathogenesis of DN remains unclear, and treatment strategies are limited.…”

Section: Pyroptosis In Diabetic Microvascular Diseasesmentioning

confidence: 99%

Targeting Pyroptosis: New Insights into the Treatment of Diabetic Microvascular Complications

Geng

Guo

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Pyroptosis is an inflammatory form of programmed cell death that is dependent on inflammatory caspases, leading to the cleavage of gasdermin D (GSDMD) and increased secretion of interleukin (IL)-1β and IL-18. Recent studies have reported that hyperglycemia-induced cellular stress stimulates pyroptosis, and different signaling pathways have been shown to play crucial roles in regulating pyroptosis. This review summarized and discussed the molecular mechanisms, regulation, and cellular effects of pyroptosis in diabetic microvascular complications, such as diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. In addition, this review aimed to provide new insights into identifying better treatments for diabetic microvascular complications.

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Animal Models and Renal Biomarkers of Diabetic Nephropathy

Cited by 15 publications

References 187 publications

Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway

Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway

Ombuin ameliorates diabetic nephropathy in rats by anti‐inflammation and antifibrosis involving Notch 1 and PPAR γ signaling pathways

Targeting Pyroptosis: New Insights into the Treatment of Diabetic Microvascular Complications

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