scholarly journals Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

2019 ◽  
Vol 67 (9) ◽  
pp. 643-661 ◽  
Author(s):  
Roman David Bülow ◽  
Peter Boor
Keyword(s):  
Extracellular Matrix ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Dynamic Structure ◽  
Renal Diseases ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Non Invasive ◽  
Ecm Proteins ◽  
Diagnostic Approaches

Kidney fibrosis is the common histological end-point of progressive, chronic kidney diseases (CKDs) regardless of the underlying etiology. The hallmark of renal fibrosis, similar to all other organs, is pathological deposition of extracellular matrix (ECM). Renal ECM is a complex network of collagens, elastin, and several glycoproteins and proteoglycans forming basal membranes and interstitial space. Several ECM functions beyond providing a scaffold and organ stability are being increasingly recognized, for example, in inflammation. ECM composition is determined by the function of each of the histological compartments of the kidney, that is, glomeruli, tubulo-interstitium, and vessels. Renal ECM is a dynamic structure undergoing remodeling, particularly during fibrosis. From a clinical perspective, ECM proteins are directly involved in several rare renal diseases and indirectly in CKD progression during renal fibrosis. ECM proteins could serve as specific non-invasive biomarkers of fibrosis and scaffolds in regenerative medicine. The gold standard and currently only specific means to measure renal fibrosis is renal biopsy, but new diagnostic approaches are appearing. Here, we discuss the localization, function, and remodeling of major renal ECM components in healthy and diseased, fibrotic kidneys and the potential use of ECM in diagnostics of renal fibrosis and in tissue engineering.

scholarly journals Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis

2019 ◽  
Vol 11 (486) ◽  
pp. eaat4865 ◽  
Author(s):  
Qinxue Sun ◽  
Maike Baues ◽  
Barbara M. Klinkhammer ◽  
Josef Ehling ◽  
Sonja Djudjaj ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Matrix Protein ◽  
Kidney Diseases ◽  
Therapeutic Interventions ◽  
Extracellular Matrix Protein ◽  
Imaging Method ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Common Endpoint ◽  
Routine Assessment

Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastin was hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agent ESMA specifically detected elastin expression in multiple mouse models of renal fibrosis and also in fibrotic human kidneys. Elastin imaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastin imaging detected ensuing fibrosis not identifiable via routine assessment of kidney function. Elastin imaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis.

scholarly journals Value of ultrasound elastography in the diagnosis of native kidney fibrosis.

2016 ◽  
Vol 18 (3) ◽  
pp. 362 ◽  
Author(s):  
Ileana Peride ◽  
Daniela Rădulescu ◽  
Andrei Niculae ◽  
Vladimir Ene ◽  
Ovidiu Gabriel Bratu ◽  
...  
Keyword(s):  
Shear Wave ◽  
Hepatic Fibrosis ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Ultrasound Elastography ◽  
Normal Kidney ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Native Kidney ◽  
Deep Location

In the last decade, ultrasound elastography, an already widely used technique in the diagnosis of hepatic fibrosis, has raised the attention of nephrologists as a potential valuable noninvasive tool for the diagnosis of renal fibrosis. Due to renal deep location and anatomic complexity, the shear wave techniques are the most appropriate elastography methods for exploring native kidneys. Recent research offers promising results, but further larger studies are required for a better standardization of this method and also for establishing reference values of normal kidney elasticity. This article reviews the studies conducted for exploring the native kidney, highlighting the advantages and limitations of ultrasound elastography for assessing fibrosis development in chronic kidney diseases.

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

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 The Secretome Analysis of Activated Human Renal Fibroblasts Revealed Beneficial Effect of the Modulation of the Secreted Peptidyl-Prolyl Cis-Trans Isomerase A in Kidney Fibrosis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1724
Author(s):  
Gry H. Dihazi ◽  
Marwa Eltoweissy ◽  
Olaf Jahn ◽  
Björn Tampe ◽  
Michael Zeisberg ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Renal Fibrosis ◽  
Cell Activation ◽  
Cell Transformation ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Kidney Fibrosis ◽  
Matrix Accumulation ◽  
The Impact

The secretome is an important mediator in the permanent process of reciprocity between cells and their environment. Components of secretome are involved in a large number of physiological mechanisms including differentiation, migration, and extracellular matrix modulation. Alteration in secretome composition may therefore trigger cell transformation, inflammation, and diseases. In the kidney, aberrant protein secretion plays a central role in cell activation and transition and in promoting renal fibrosis onset and progression. Using comparative proteomic analyses, we investigated in the present study the impact of cell transition on renal fibroblast cells secretome. Human renal cell lines were stimulated with profibrotic hormones and cytokines, and alterations in secretome were investigated using proteomic approaches. We identified protein signatures specific for the fibrotic phenotype and investigated the impact of modeling secretome proteins on extra cellular matrix accumulation. The secretion of peptidyl-prolyl cis-trans isomerase A (PPIA) was demonstrated to be associated with fibrosis phenotype. We showed that the in-vitro inhibition of PPIA with ciclosporin A (CsA) resulted in downregulation of PPIA and fibronectin (FN1) expression and significantly reduced their secretion. Knockdown studies of PPIA in a three-dimensional (3D) cell culture model significantly impaired the secretion and accumulation of the extracellular matrix (ECM), suggesting a positive therapeutic effect on renal fibrosis progression.

scholarly journals SOX9 is required for kidney fibrosis and regulates NAV3 to control renal myofibroblast function in mice and humans

2019 ◽  
Author(s):  
Sayyid Raza ◽  
Elliot Jokl ◽  
James Pritchett ◽  
Katherine Martin ◽  
Kim Su ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Kidney Diseases ◽  
Pharmacological Intervention ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Genome Wide ◽  
Common Endpoint ◽  
Vitro Model ◽  
Novel Target

AbstractRenal fibrosis is a common endpoint for many chronic kidney diseases. Extracellular matrix (ECM) from myofibroblasts causes progressive scarring and organ failure. The mechanisms underlying fibrogenesis and how it is sustained are incompletely understood. Here, we show that the transcription factor, Sex determining region Y-box 9 (SOX9), is required for kidney fibrosis. From genome-wide analysis we identify Neuron navigator 3 (NAV3) downstream of SOX9. NAV3 was upregulated in kidney disease in patients and following renal injury in mice colocalised with SOX9. By establishing an in vitro model of renal pericyte transition to myofibroblast we demonstrated that NAV3 is required for multiple aspects of fibrogenesis including actin polymerization linked to cell migration and sustaining SOX9 and active YAP1 levels. In summary, our work discovers novel SOX9-NAV3-YAP1/SOX9 circuitry as a new mechanism to explain the progression of kidney fibrosis and points to NAV3 as a novel target for pharmacological intervention.

scholarly journals Mesenchymal stem cells ameliorate renal fibrosis by galectin-3/Akt/GSK3β/Snail signaling pathway in adenine-induced nephropathy rat

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huajun Tang ◽  
Peiyue Zhang ◽  
Lianlin Zeng ◽  
Yu Zhao ◽  
Libo Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Lentiviral Vector ◽  
Kidney Diseases ◽  
Collagen Type I ◽  
Type I ◽  
Chronic Kidney Diseases ◽  
Galectin 3 ◽  
Tgf Β1 ◽  
Sirius Red

Abstract Background Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics. Methods TIF model was induced by adenine gavage. Bone marrow-derived MSCs was injected by tail vein after modeling. Renal function and fibrosis related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. Further possible mechanism was explored by transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with lentiviral vector. Results MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-β1, Kim-1, p-Smad2/3, IL-6, IL-1β, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-β1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt, p-GSK3β and snail in TGF-β1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3β and snail. Conclusion The mechanism of MSCs anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3β/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.

scholarly journals IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target

2020 ◽  
Vol 21 (3) ◽  
pp. 1009
Author(s):  
Tian-Yu Lin ◽  
Yu-Hsiang Hsu
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Renal Fibrosis ◽  
Inflammatory Mediator ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Pro Inflammatory Cytokines

Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.

Integrated In-silico Analysis to Study the Role of microRNAs in the Detection of Chronic Kidney Diseases

2020 ◽  
Vol 15 (2) ◽  
pp. 144-154
Author(s):  
Amina Khan ◽  
Andleeb Zahra ◽  
Sana Mumtaz ◽  
M. Qaiser Fatmi ◽  
Muhammad J. Khan
Keyword(s):  
Target Genes ◽  
Kidney Development ◽  
Kidney Diseases ◽  
In Silico Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Renal Diseases ◽  
P Value ◽  
Chronic Kidney Diseases

Background: MicroRNAs (miRNAs) play an important role in the pathogenesis of various renal diseases, including Chronic Kidney Diseases (CKD). CKD refers to the gradual loss of kidney function with the declining Glomerular Functional Rate (GFR). Objective: This study focused on the regulatory mechanism of miRNA to control gene expression in CKD. Methods: In this context, two lists of Differentially Expressed Genes (DEGs) were obtained; one from the three selected experiments by setting a cutoff p-value of <0.05 (List A), and one from a list of target genes of miRNAs (List B). Both lists were then compared to get a common dataset of 33 miRNAs, each had a set of DEGs i.e. both up-regulated and down-regulated genes (List C). These data were subjected to functional enrichment analysis, network illustration, and gene homology studies. Results: This study confirmed the active participation of various miRNAs i.e. hsa -miR-15a-5p, hsa-miR-195-5p, hsa-miR-365-3p, hsa-miR-30a-5p, hsa-miR-124-3p, hsa-miR-200b-3p, and hsamiR- 429 in the dysregulation of genes involved in kidney development and function. Integrated analyses depicted that miRNAs modulated renal development, homeostasis, various metabolic processes, immune responses, and ion transport activities. Furthermore, homology studies of miRNA-mRNA hybrid highlighted the effect of partial complementary binding pattern on the regulation of genes by miRNA. Conclusion: The study highlighted the great values of miRNAs as biomarkers in kidney diseases. In addition, the need for further investigations on miRNA-based studies is also commended in the development of diagnostic, prognostic, and therapeutic tools for renal diseases.

Differential diagnosis of urinary syndrome

2020 ◽  
pp. 48-59
Author(s):  
Ashot Karapetyan
Keyword(s):  
Differential Diagnosis ◽  
Urinary Tract ◽  
Interstitial Nephritis ◽  
Clinical Examination ◽  
Kidney Diseases ◽  
Vascular Anomalies ◽  
Urine Test ◽  
Chronic Kidney Diseases ◽  
Diagnostic Approaches ◽  
Renal Vascular

The article presents the clinician's view on general diagnostic and differential diagnostic approaches when analyzing data of the urine test in patients with nephrological, therapeutic and urological pathology. Features of the urinary syndrome are examined in detail depending on the presence, degree and severity of haematuria, leukocyturia, proteinuria, cylindruria in various diseases. Moments of diagnosis and clinical examination of patients with urolithiasis, kidney and urinary tract tumors, urinary tract tuberculosis, renal vascular anomalies, cystic dysplasia, and nephroptosis are described in detail in addition to traditional chronic kidney diseases (glomerulonephritis, pyelonephritis, interstitial nephritis).

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