scholarly journals Renoprotective Role of Hypoxia-Inducible Factors and the Mechanism

2021 ◽  
pp. 1-13
Author(s):  
Qiu-Yu Li ◽  
Fei Liu ◽  
Xiaoxiao Tang ◽  
Haidong Fu ◽  
Jianhua Mao
Keyword(s):  
Target Genes ◽  
Renal Tumor ◽  
Kidney Diseases ◽  
Acute Hypoxia ◽  
Hypoxia Inducible Factors ◽  
Tubular Injury ◽  
Physiological Mechanisms ◽  
Chronic Kidney Diseases ◽  
Almost All

<b><i>Background:</i></b> The kidney requires abundant blood supply, and oxygen is transmitted by diffusion through blood vessels. Most physiological metabolism of the kidney depends on oxygen, so it is very sensitive to oxygen. An increasing pool of evidence suggests that hypoxia is involved in almost all acute and chronic kidney diseases (CKDs). Vascular damage, tubular injury, and fibrosis are the main pathologies associated during hypoxia. Hypoxia-inducible factors (HIFs) are the main mediators during hypoxia, but their functions remain controversial. This article reviewed recent studies and described its mechanisms on renoprotection. <b><i>Summary:</i></b> HIF is degraded rapidly during under normal oxygen. But under hypoxia, HIFs accumulate and many target genes are regulated by HIFs. Homeostasis during injury is maintained through these genes. Pretreatment of HIF can protect the kidney from acute hypoxia and can improve repair, but HIF’s role in CKD and in renal tumor is still controversial. Due to its mechanism in kidney disease, many drugs toward HIFs are widely researched, even some of which have been used in clinical or in clinical research. <b><i>Key Messages:</i></b> In this review, we described the known physiological mechanisms, target genes, and renal protective roles of HIFs, and we discussed several drugs that are researched due to such renal protective roles.

scholarly journals Hypoxia and Hypoxia-Inducible Factors in Kidney Injury and Repair

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 207 ◽  
Author(s):  
Shaoqun Shu ◽  
Ying Wang ◽  
Meiling Zheng ◽  
Zhiwen Liu ◽  
Juan Cai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Kidney Disease ◽  
Target Genes ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Hypoxia Inducible Factors ◽  
Experimental Conditions ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Injury And Repair

Acute kidney injury (AKI) is a major kidney disease characterized by an abrupt loss of renal function. Accumulating evidence indicates that incomplete or maladaptive repair after AKI can result in kidney fibrosis and the development and progression of chronic kidney disease (CKD). Hypoxia, a condition of insufficient supply of oxygen to cells and tissues, occurs in both acute and chronic kidney diseases under a variety of clinical and experimental conditions. Hypoxia-inducible factors (HIFs) are the “master” transcription factors responsible for gene expression in hypoxia. Recent researches demonstrate that HIFs play an important role in kidney injury and repair by regulating HIF target genes, including microRNAs. However, there are controversies regarding the pathological roles of HIFs in kidney injury and repair. In this review, we describe the regulation, expression, and functions of HIFs, and their target genes and related functions. We also discuss the involvement of HIFs in AKI and kidney repair, presenting HIFs as effective therapeutic targets.

scholarly journals Kidney organoid systems for studies of immune-mediated kidney diseases: challenges and opportunities

2021 ◽  
Author(s):  
Melissa C. Stein ◽  
Fabian Braun ◽  
Christian F. Krebs ◽  
Madeleine J. Bunders
Keyword(s):  
Kidney Diseases ◽  
Three Dimensional ◽  
Renal Tissue ◽  
Chronic Kidney Diseases ◽  
Immune Mediated ◽  
Primary Epithelial Cell ◽  
Challenges And Opportunities ◽  
Underlying Mechanisms ◽  
Global Population

AbstractAcute and chronic kidney diseases are major contributors to morbidity and mortality in the global population. Many nephropathies are considered to be immune-mediated with dysregulated immune responses playing an important role in the pathogenesis. At present, targeted approaches for many kidney diseases are still lacking, as the underlying mechanisms remain insufficiently understood. With the recent development of organoids—a three-dimensional, multicellular culture system, which recapitulates important aspects of human tissues—new opportunities to investigate interactions between renal cells and immune cells in the pathogenesis of kidney diseases arise. To date, kidney organoid systems, which reflect the structure and closer resemble critical aspects of the organ, have been established. Here, we highlight the recent advances in the development of kidney organoid models, including pluripotent stem cell-derived kidney organoids and primary epithelial cell-based tubuloids. The employment and further required advances of current organoid models are discussed to investigate the role of the immune system in renal tissue development, regeneration, and inflammation to identify targets for the development of novel therapeutic approaches of immune-mediated kidney diseases.

The Role of the CX3CL1-CX3CR1 Axis in Renal Disease

2021 ◽  
Author(s):  
Diana Hamdan ◽  
Lisa A. Robinson
Keyword(s):  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Transmembrane Protein ◽  
Soluble Form ◽  
Protective Effects ◽  
Chronic Kidney Diseases ◽  
The Family ◽  
Soluble Species ◽  
And Function

Excessive infiltration of immune cells into the kidney is a key feature of acute and chronic kidney diseases. The family of chemokines are key drivers of this process. CX3CL1 (fractalkine) is one of two unique chemokines synthesized as a transmembrane protein which undergoes proteolytic cleavage to generate a soluble species. Through interacting with its cognate receptor, CX3CR1, CX3CL1 was originally shown to act as a conventional chemoattractant in the soluble form, and as an adhesion molecule in the transmembrane form. Since then, other functions of CX3CL1 beyond leukocyte recruitment have been described, including cell survival, immunosurveillance, and cell-mediated cytotoxicity. This review summarizes diverse roles of CX3CL1 in kidney disease and potential uses as a therapeutic target and novel biomarker. As the CX3CL1-CX3CR1 axis has been shown to contribute to both detrimental and protective effects in various kidney diseases, a thorough understanding of how the expression and function of CX3CL1 are regulated is needed to unlock its therapeutic potential.

scholarly journals Characterization of IL-19, -20, and -24 in acute and chronic kidney diseases reveals a pro-fibrotic role of IL-24

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Domonkos Pap ◽  
Apor Veres-Székely ◽  
Beáta Szebeni ◽  
Réka Rokonay ◽  
Anna Ónody ◽  
...  
Keyword(s):  
Animal Models ◽  
Mononuclear Cells ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Renal Diseases ◽  
Peripheral Blood Mononuclear ◽  
Chronic Kidney Diseases ◽  
Tgf Β1

Abstract Background Recently, the role of IL-19, IL-20 and IL-24 has been reported in renal disorders. However, still little is known about their biological role. Methods Localization of IL-20RB was determined in human biopsies and in the kidneys of mice that underwent unilateral ureteral obstruction (UUO). Renal Il19, Il20 and Il24 expression was determined in ischemia/reperfusion, lipopolysaccharide, streptozotocin, or UUO induced animal models of kidney diseases. The effects of H2O2, LPS, TGF-β1, PDGF-B and IL-1β on IL19, IL20 and IL24 expression was determined in peripheral blood mononuclear cells (PBMCs). The extents of extracellular matrix (ECM) and α-SMA, Tgfb1, Pdgfb, and Ctgf expression were determined in the kidneys of Il20rb knockout (KO) and wild type (WT) mice following UUO. The effect of IL-24 was also examined on HK-2 tubular epithelial cells and NRK49F renal fibroblasts. Results IL-20RB was present in the renal biopsies of patients with lupus nephritis, IgA and diabetic nephropathy. Amount of IL-20RB increased in the kidneys of mice underwent UUO. The expression of Il19, Il20 and Il24 increased in the animal models of various kidney diseases. IL-1β, H2O2 and LPS induced the IL19, IL20 and IL24 expression of PBMCs. The extent of ECM, α-SMA, fibronectin, Tgfb1, Pdgfb, and Ctgf expression was lower in the kidney of Il20rb KO compared to WT mice following UUO. IL-24 treatment induced the apoptosis and TGF-β1, PDGF-B, CTGF expression of HK-2 cells. Conclusions Our data confirmed the significance of IL-19, IL-20 and IL-24 in the pathomechanism of renal diseases. Furthermore, we were the first to demonstrate the pro-fibrotic effect of IL-24.

scholarly journals Lack of miRNA-17 family mediates high glucose-induced PAR-1 up-regulation in glomerular mesangial cells

2021 ◽  
Author(s):  
Zhuang-Zhuang Tang ◽  
Pan-Pan Gu ◽  
Xiao-Fei An ◽  
Ling-Shan Gou ◽  
Yao-Wu Liu
Keyword(s):  
High Glucose ◽  
Mesangial Cells ◽  
Kidney Diseases ◽  
Mrna Level ◽  
Glomerular Mesangial Cells ◽  
Chronic Kidney Diseases ◽  
Protein Levels ◽  
Normal Glucose ◽  
Protease Activated Receptor 1

Abstract Up-regulation of thrombin receptor protease-activated receptor 1 (PAR-1) is verified to contribute to chronic kidney diseases, including diabetic nephropathy, however, the mechanisms are still unclear. In this study, we investigated the effect of PAR-1 on high glucose-induced proliferation of human glomerular mesangial cells (HMCs), and explored the mechanism of PAR-1 up-regulation from alteration of microRNAs. We found that high glucose stimulated proliferation of the mesangial cells whereas PAR-1 inhibition with vorapaxar attenuated the cell proliferation. Moreover, high glucose up-regulated PAR-1 in mRNA level and protein expression while did not affect the enzymatic activity of thrombin in HMCs after 48 h culture. Then high glucose induced PAR-1 elevation was likely due to the alteration of the transcription or post-transcriptional processing. It was found that miR-17 family members including miR-17-5p, -20a-5p, and − 93-5p were markedly decreased among the eight detected microRNAs only in high glucose-cultured HMCs, but miR-129-5p, miR-181a-5p, and miR-181b-5p were markedly decreased in both high glucose-cultured HMCs and osmotic press control compared with normal glucose culture. So miR-20a was selected to confirm the role of miR-17 family on PAR-1 up-regulation, finding that miR-20a-5p overexpression reversed the up-regulation of PAR-1 in mRNA and protein levels induced by high glucose in HMCs. In summary, our finding indicated that PAR-1 up-regulation mediated proliferation of glomerular mesangial cells induced by high glucose, and deficiency of miR-17 family resulted in PAR-1 up-regulation.

scholarly journals The role of metabolic acidosis in chronic kidney diseases

2010 ◽  
Vol 4 (3) ◽  
pp. 367-372
Author(s):  
James C. M. Chan
Keyword(s):  
Chronic Kidney Disease ◽  
Metabolic Acidosis ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Original Research ◽  
Due Diligence ◽  
Acid Base ◽  
Chronic Kidney Diseases ◽  
Balance Development

Abstract Background and objectives: This review focuses on three areas, basic acid-base physiology especially concerning hydrogen ion balance, development of acidosis in chronic kidney disease (CKD), and the consequences of acidosis. We highlight what is well established, what is less certain, and what is unknown. Method and results: The literature on acidosis in CKD were searched from 2004 to 2010 utilizing PubMed, Google Scholar, and Ovid to augment the classic work on acid base physiology over the past three decades. The original research in endogenous acid production and net acid excretion were reviewed. Touching upon the development of metabolic acidosis in CKD, we focused on the consequences of chronic metabolic acidosis on growth and other important variables. Finally, we recognize the significant issue of patients’ medical non-compliance and presented treatment strategy to counter this problem. Conclusion: The correction of acidosis in chronic kidney disease needs no advocacy. The case is made conclusively. Patient non-compliance because of the medication that needs to be taken several times a day is a problem, requiring due diligence.

scholarly journals Measurement of Inflammation-Related Biomarkers in Different Chronic Kidney Diseases in Humans: Role of Aging and Gender?

2021 ◽  
Vol 20 (4) ◽  
Author(s):  
Abdulla Ahmad ◽  
Mohammed Ajeel ◽  
Karam Aldabbagh
Keyword(s):  
Plasma Level ◽  
Total Protein ◽  
Kidney Diseases ◽  
Chronic Glomerulonephritis ◽  
Age Difference ◽  
Bioactive Substances ◽  
Chronic Kidney Diseases ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin

INTRODUCTION: Chronic kidney disease (CKD) is a worldwide health problem which becomes a substantial emerging cause of morbidity. The inflammation can be resulted via different mechanisms in different kidney diseases including the imbalance of proinflammatory/anti-inflammatory biomarkers levels. This study aimed to measure the level of physiological bioactive substances as inflammation-related biomarkers in different CKD and to investigate whether gender or aging is critical in these measurements. MATERIALS AND METHODS: 84 persons (19 healthy, 29 chronic glomerulonephritis, 26 diabetic nephropathy, 6 benign nephrosclerosis, 4 lupus nephritis) were enrolled in this study. The inflammation progression degree in CKD was estimated by measuring the plasma level of neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein 1 (MCP1), and clusterin (CLU) using ELISA. Serum total protein, urea and creatinine were measured using an automatic analyzer. RESULTS: Plasma level of urea and creatinine was increased while total protein level was decreased in all the patients compared to control participants. The level of NGAL, MCP1 and CLU was significantly increased in all the kidney diseases compared to controls. In addition, there were no differences in the level of inflammation-related markers between women and men. Moreover, the levels of inflammatory markers were increased in the kidney diseases regardless of the age difference. CONCLUSIONS: This study showed that the physiological bioactive substances NGAL, MCP1 and CLU can be increased in renal pathologies and considered as good indicators of progression of inflammation in chronic kidney diseases, with no role of gender and age in their increment plasma levels.

scholarly journals FP092NOVEL ROLE OF IL-20 CYTOKINE SUBFAMILY IN THE PATHOGENESIS OF CHRONIC KIDNEY DISEASES

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i78-i78
Author(s):  
Domonkos Pap ◽  
Apor Veres-Székely ◽  
Rita Lippai ◽  
Reka Rokonay ◽  
Istvan Marton Takacs ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Chronic Kidney Diseases

COLONIC MICROBIOTA AND CHRONIC KIDNEY DISEASES INTESTINAL MICROBIOTA AND CHRONIC KIDNEY DISEASE. PART II

2019 ◽  
Vol 23 (1) ◽  
pp. 18-31 ◽  
Author(s):  
B. G. Lukichev ◽  
A. Sh. Rumyantsev ◽  
I. Yu. Panina ◽  
V. Akimenko
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Intestinal Microbiota ◽  
Kidney Diseases ◽  
Biologically Active ◽  
Chronic Kidney Diseases ◽  
Mechanical Removal ◽  
Starting Point ◽  
Active Substances

Interest in studying the role of the gastrointestinal tract in maintaining homeostasis in chronic kidney disease is a traditional one. It served, in particular, as a starting point for the creation of enterosorbents. However, if earlier the main attention was paid to the mechanical removal of a number of potentially dangerous biologically active substances, recently an intestinal microbiota has become an object of interest. The first part of the review of the literature on this topic is devoted to questions of terminology, the normal physiology of the colon microbiota. A detailed description of dysbiosis is given. The features of the main groups of microorganisms are reflected. The hypothetical and confirmed interrelations of the intestine-kidney axis are presented. The pathogenetic mechanisms of the influence of colon dysbiosis on the processes of local and systemic inflammation are discussed. The influence of dysbiosis on the state of the kidney parenchyma and its participation in the progression of CKD are debated.

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