Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy

Yang, Jing; Liu, Zhangsuo

doi:10.3389/fendo.2022.816400

Cited by 90 publications

(58 citation statements)

References 269 publications

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“…The pathophysiology of both DR and diabetic nephropathy is similar. The development of DR and diabetic nephropathy influences and promotes each other, which supports the view that the two diseases share a common etiological basis, and emphasizes that the treatment and care of DR should be combined with a multidisciplinary integrated treatment management model [ 35 ].…”

Section: Discussionmentioning

confidence: 84%

A prediction model for worsening diabetic retinopathy after panretinal photocoagulation

Lei

et al. 2022

Diabetol Metab Syndr

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Background As one of the severe complications of diabetes mellitus, diabetic retinopathy (DR) is the leading cause of blindness in the working age worldwide. Although panretinal photocoagulation (PRP) was standard treatment, PRP-treated DR still has a high risk of progression. Hence, this study aimed to assess the risk factors and establish a model for predicting worsening diabetic retinopathy (DR-worsening) within five years after PRP. Methods Patients who were diagnosed with severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and treated with PRP were included, and those patients were randomly assigned to either a training or validation cohort. The multivariate logistic regression analysis was used to screen potential risk factors for DR-worsening in the training cohort. Then the model was established after including significant independent risk factors and further validated using discrimination and calibration. Results A total of 271 patients were included, and 56.46% of patients had an outcome of DR-worsening. In the training cohort (n = 135), age (odds ratio [OR] = 0.94, 95% confidence interval [CI] 0.90–0.98), baseline best corrected visual acuity (logMAR) (OR = 10.74, 95% CI 1.84–62.52), diabetic nephropathy (OR = 9.32, 95% CI 1.49–58.46), and hyperlipidemia (OR = 3.34, 95% CI 1.05–10.66) were screened out as the independent risk factors, which were incorporated into the predictive model. The area under the receiver operating characteristic curve and calibration slope in the training and validation cohort were 0.79, 0.96 (95% CI 0.60–1.31), and 0.79, 1.00 (95% CI 0.66–1.34), respectively. Two risk groups were developed depending on the best cut-off value of the predicted probability, and the actual probability was 34.90% and 82.79% in the low-risk and high-risk groups, respectively (P < 0.001). Conclusions This study developed and internally validated a new model to predict the probability of DR-worsening after PRP treatment within five years. The model can be used as a rapid risk assessment system for clinical prediction of DR-worsening and identify individuals at a high risk of DR-worsening at an early stage and prescribe additional treatment.

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Section: Discussionmentioning

confidence: 84%

A prediction model for worsening diabetic retinopathy after panretinal photocoagulation

Lei

et al. 2022

Diabetol Metab Syndr

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“…It is of note that crosstalk among podocytes and other cell types in the kidney has been demonstrated in the literature. For example, during CKD progression, vascular endothelial growth factor (VEGF)-A/C and angiopoietin-1 are secreted by podocytes, which results in glomerular endothelial cell dysfunction and albuminuria [ 39 , 40 , 41 ]. Moreover, podocyte–mesangial cell communication has also been reported.…”

Section: Discussionmentioning

confidence: 99%

Paracrine Effects of Renal Proximal Tubular Epithelial Cells on Podocyte Injury under Hypoxic Conditions Are Mediated by Arginase-II and TGF-β1

Potenza

Ajalbert

et al. 2023

IJMS

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Hypoxia is an important risk for renal disease. The mitochondrial enzyme arginase-II (Arg-II) is expressed and/or induced by hypoxia in proximal tubular epithelial cells (PTECs) and in podocytes, leading to cellular damage. Because PTECs are vulnerable to hypoxia and located in proximity to podocytes, we examined the role of Arg-II in the crosstalk of PTECs under hypoxic conditions with podocytes. A human PTEC cell line (HK2) and a human podocyte cell line (AB8/13) were cultured. Arg-ii gene was ablated by CRISPR/Case9 in both cell types. HK2 cells were exposed to normoxia (21% O2) or hypoxia (1% O2) for 48 h. Conditioned medium (CM) was collected and transferred to the podocytes. Podocyte injuries were then analyzed. Hypoxic (not normoxic) HK2-CM caused cytoskeletal derangement, cell apoptosis, and increased Arg-II levels in differentiated podocytes. These effects were absent when arg-ii in HK2 was ablated. The detrimental effects of the hypoxic HK2-CM were prevented by TGF-β1 type-I receptor blocker SB431542. Indeed, TGF-β1 levels in hypoxic HK2-CM (but not arg-ii−/−-HK2-CM) were increased. Furthermore, the detrimental effects of TGF-β1 on podocytes were prevented in arg-ii−/−-podocytes. This study demonstrates crosstalk between PTECs and podocytes through the Arg-II-TGF-β1 cascade, which may contribute to hypoxia-induced podocyte damage.

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“…Diabetic nephropathy and diabetic retinopathy have the same pathogenesis, which is caused by the dysfunction of microvascular endothelial function ( 178 ). Consistent with DFUs, hyperglycemia through various pathways such as the polyol pathway, the AGE/receptor for AGE axis and the PKC pathway increases ROS production, causes oxidative stress and a series of inflammatory responses, and eventually leads to the accumulation of AGEs and endothelial dysfunction.…”

Section: Shared Mechanisms Between Diabetic Complications and Dfusmentioning

confidence: 99%

Role of ceramides in diabetic foot ulcers (Review)

et al. 2023

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diabetes mellitus (dM) is a metabolic disorder, which if not managed properly, can lead to serious health problems over time and impose significant financial burden on the patient, their family and society as a whole. The study of this disease and the underlying biological mechanism is gaining momentum. Multiple pieces of conclusive evidence show that ceramides are involved in the occurrence and development of diabetes. The present review focuses on the function of ceramides, a type of sphingolipid signaling molecule, to provide a brief description of ceramides and their metabolism, discuss the significant roles of ceramides in the healthy skin barrier, and speculate on the potential involvement of ceramides in the pathogenesis and development of diabetic foot ulcers (dFUs). Understanding these aspects of this disease more thoroughly is crucial to establish how ceramides contribute to the etiology of diabetic foot infections and identify possible therapeutic targets for the treatment of dFUs. Contents1. Introduction 2. Biosynthesis and degradation of ceramides 3. Ceramides in the skin 4. ceramides and dFUs 5. ceramides and vessels 6. ceramides and diabetes 7. ceramides and atherosclerosis 8. Mechanism of ceramides in diabetes 9. Mechanism of ceramides in atherosclerosis 10. Shared mechanisms between diabetic complications and dFUs 11. conclusions

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Mechanistic Pathogenesis of Endothelial Dysfunction in Diabetic Nephropathy and Retinopathy

Cited by 90 publications

References 269 publications

A prediction model for worsening diabetic retinopathy after panretinal photocoagulation

A prediction model for worsening diabetic retinopathy after panretinal photocoagulation

Paracrine Effects of Renal Proximal Tubular Epithelial Cells on Podocyte Injury under Hypoxic Conditions Are Mediated by Arginase-II and TGF-β1

Role of ceramides in diabetic foot ulcers (Review)

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