The Role of Peroxisome Proliferator-Activated Receptors in Kidney Diseases

Gao, Jianjun; Gu, Zhaoyan

doi:10.3389/fphar.2022.832732

Cited by 27 publications

(19 citation statements)

References 117 publications

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“…Activated PPAR α signi cantly reduced triglyceride levels, and moderately reduced total cholesterol levels and low-density lipoprotein cholesterol levels, thus increasing high-density lipoprotein cholesterol levels [20]. PPAR α is expressed in kidney podocytes, and activated PPAR α is able to reduce albuminuria and improve insulin resistance [21]. Activation of PPAR α may be a favorable factor for DN progression.…”

Section: Discussionmentioning

confidence: 99%

Temporal Alteration of Serum Bilirubin Levels and its Renoprotective Effects in Diabetic Nephropathy: Exploring the Hormonal Mechanisms

Cao

Wei

et al. 2023

Preprint

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Objective This current study represents a novel endeavor to scrutinize the correlation between the temporal alteration in serum total bilirubin (TBIL) concentrations and the rate of estimated glomerular filtration rate (eGFR). Additionally, this study aims to probe the plausible molecular mechanism underpinning the renoprotective effects of bilirubin concerning its hormonal characteristics. Materials and Methods In this study, a cohort of 103 patients diagnosed with DN and receiving medical care at Dongzhimen Hospital were recruited and monitored over a period of 2–7 years. The progression of DN was ascertained using a threshold of eGFR decline > -5.48%/year. To assess the relationship between the annual change in serum TBIL levels (%/year) and the slope of eGFR, multivariate binary logistic regression analysis was employed. Furthermore, the ROC curve analysis was employed to determine the cut-off value for TBIL levels (%/year). Results The use of multivariate binary logistic regression models revealed that serum TBIL levels (%/year) exhibited a significant correlation with the slope of eGFR. Moreover, the ROC curve analysis indicated a cut-off value of -6.729%/year for TBIL levels (%/year) with a sensitivity of 0.75 and specificity of 0.603, in diagnosing eGFR decline >-5.48%/year. Conclusions The findings of this study suggest that the sustained elevation of serum bilirubin concentration within the physiological range can effectively retard the progression of diabetic nephropathy (DN). Furthermore, the hormonal attributes of bilirubin may underlie its renoprotective effects.

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Section: Discussionmentioning

confidence: 99%

Temporal Alteration of Serum Bilirubin Levels and its Renoprotective Effects in Diabetic Nephropathy: Exploring the Hormonal Mechanisms

Cao

Wei

et al. 2023

Preprint

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“…As a nuclear receptor transcriptional factor, PPARβ/δ is involved in many physiological and pathological processes [ 1 , 2 , 3 ]. Increasing evidence has suggested that PPARβ/δ plays an important role in the regulation of inflammatory responses [ 10 , 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…PPARβ/δ is a ligand-activated transcription factor that belongs to the nuclear hormone receptor family [ 1 , 2 , 3 ]. PPARβ/δ is ubiquitously expressed in almost all examined tissues.…”

Section: Introductionmentioning

confidence: 99%

PPARβ/δ Augments IL-1β-Induced COX-2 Expression and PGE2 Biosynthesis in Human Mesangial Cells via the Activation of SIRT1

Cao

et al. 2022

Metabolites

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Peroxisome proliferator-activated receptor β/δ (PPARβ/δ), a ligand-activated nuclear receptor, regulates lipid and glucose metabolism and inflammation. PPARβ/δ can exert an anti-inflammatory effect by suppressing proinflammatory cytokine production. Cyclooxygenase-2 (COX-2)-triggered inflammation plays a crucial role in the development of many inflammatory diseases, including glomerulonephritis. However, the effect of PPARβ/δ on the expression of COX-2 in the kidney has not been fully elucidated. The present study showed that PPARβ/δ was functionally expressed in human mesangial cells (hMCs), where its expression was increased by interleukin-1β (IL-1β) treatment concomitant with enhanced COX-2 expression and prostaglandin E2 (PGE2) biosynthesis. The treatment of hMCs with GW0742, a selective agonist of PPARβ/δ, or the overexpression of PPARβ/δ via an adenovirus-mediated approach significantly increased COX-2 expression and PGE2 production. PPARβ/δ could further augment the IL-1β-induced COX-2 expression and PGE2 production in hMCs. Moreover, both PPARβ/δ activation and overexpression markedly increased sirtuin 1 (SIRT1) expression. The inhibition or knockdown of SIRT1 significantly attenuated the effects of PPARβ/δ on the IL-1β-induced expression of COX-2 and PGE2 biosynthesis. Taken together, PPARβ/δ could augment the IL-1β-induced COX-2 expression and PGE2 production in hMCs via the SIRT1 pathway. Given the critical role of COX-2 in glomerulonephritis, PPARβ/δ may represent a novel target for the treatment of renal inflammatory diseases.

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“…Treatment of T2DM requires alleviation of insulin resistance and correction of dyslipidemia while preserving pancreatic β-cell function [ 4 ]. Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated nuclear receptor, the activation of which can heighten the sensitivity of peripheral tissues to insulin and therefore increase glucose uptake and utilization in muscle, promote adipocyte remodeling, fatty acid decomposition, and synthesis in adipose tissue while inhibiting gluconeogenesis in liver [ 6 , 7 ]. Thiazolidinediones (TZDs), PPARγ agonists, are crucial to modulating glucose and lipid metabolic homeostasis [ 8 , 9 ] and mainly act by increasing insulin sensitivity [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

The Potential Roles of Post-Translational Modifications of PPARγ in Treating Diabetes

Zhang

Yin

et al. 2022

Biomolecules

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The number of patients with type 2 diabetes mellitus (T2DM), which is mainly characterized by insulin resistance and insulin secretion deficiency, has been soaring in recent years. Accompanied by many other metabolic syndromes, such as cardiovascular diseases, T2DM represents a big challenge to public health and economic development. Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated nuclear receptor that is critical in regulating glucose and lipid metabolism, has been developed as a powerful drug target for T2DM, such as thiazolidinediones (TZDs). Despite thiazolidinediones (TZDs), a class of PPARγ agonists, having been proven to be potent insulin sensitizers, their use is restricted in the treatment of diabetes for their adverse effects. Post-translational modifications (PTMs) have shed light on the selective activation of PPARγ, which shows great potential to circumvent TZDs’ side effects while maintaining insulin sensitization. In this review, we will focus on the potential effects of PTMs of PPARγ on treating T2DM in terms of phosphorylation, acetylation, ubiquitination, SUMOylation, O-GlcNAcylation, and S-nitrosylation. A better understanding of PTMs of PPARγ will help to design a new generation of safer compounds targeting PPARγ to treat type 2 diabetes.

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The Role of Peroxisome Proliferator-Activated Receptors in Kidney Diseases

Cited by 27 publications

References 117 publications

Temporal Alteration of Serum Bilirubin Levels and its Renoprotective Effects in Diabetic Nephropathy: Exploring the Hormonal Mechanisms

Temporal Alteration of Serum Bilirubin Levels and its Renoprotective Effects in Diabetic Nephropathy: Exploring the Hormonal Mechanisms

PPARβ/δ Augments IL-1β-Induced COX-2 Expression and PGE2 Biosynthesis in Human Mesangial Cells via the Activation of SIRT1

The Potential Roles of Post-Translational Modifications of PPARγ in Treating Diabetes

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