Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
3.7
4.7
Journals
Biomedicines
Special Issues
Glomerular Microenvironment: Cellular Stress in Chronic Kidney Disease
share announcement

Glomerular Microenvironment: Cellular Stress in Chronic Kidney Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 18274

Special Issue Editor

Dr. Hans-Kristian Lorenzo

E-Mail Website
Guest Editor
1. Faculté de Médecine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France
2. Bicêtre Hospital, Department of Nephrology, 94270 Le Kremlin-Bicêtre, France
3. INSERM U1197, 14 Avenue Paul Vaillant Couturier, 94807 Villejuif, France
Interests: cell death; senescence; autophagy; DNA damage; stem cells; pathogenesis of renal disorder; molecular medicine; immunology of transplantation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) is a global public health problem that affects people from all segments of society. The renal glomerulus, and in particular the filtration barrier, is the main target of such disorders. Its structure constitutes a special and unique microenvironment whose integrity is maintained by the molecular interaction between three central components: the endothelial cell, the basement membrane, and the podocytes. This exquisite architecture must be finely preserved because its destabilization, through extraordinarily complex molecular mechanisms, can lead to the appearance of severe proteinuria.

The structural complexity of the glomerular microenvironment limits the availability of reliable experimental models. In this sense, recent advances in regenerative medicine, as well as the design of microfluidic platforms or other devices, constitute a plethora of promising models for the study of CKD.

This Special Issue aims to serve as a report on the state of the art of basic and translational research in the field of the pathogenesis of nephrotic syndrome: molecular mechanisms as well as new experimental models.

Dr. Hans-Kristian Lorenzo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glomerular filtration barrier
  • chronic kidney disease
  • nephrotic syndrome
  • podocytes
  • glomerular cell stress
  • stem cells
  • organoids
  • regenerative medicine

Related Special Issue

Published Papers (5 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 6044 KiB  
Article
BET Proteins Regulate Expression of Osr1 in Early Kidney Development
by Janina Schreiber, Nastassia Liaukouskaya, Lars Fuhrmann, Alexander-Thomas Hauser, Manfred Jung, Tobias B. Huber and Nicola Wanner
Biomedicines 2021, 9(12), 1878; https://doi.org/10.3390/biomedicines9121878 - 10 Dec 2021
Cited by 1 | Viewed by 2703
Abstract
In utero renal development is subject to maternal metabolic and environmental influences affecting long-term renal function and the risk of developing chronic kidney failure and cardiovascular disease. Epigenetic processes have been implicated in the orchestration of renal development and prenatal programming of nephron [...] Read more.
In utero renal development is subject to maternal metabolic and environmental influences affecting long-term renal function and the risk of developing chronic kidney failure and cardiovascular disease. Epigenetic processes have been implicated in the orchestration of renal development and prenatal programming of nephron number. However, the role of many epigenetic modifiers for kidney development is still unclear. Bromodomain and extra-terminal domain (BET) proteins act as histone acetylation reader molecules and promote gene transcription. BET family members Brd2, Brd3 and Brd4 are expressed in the nephrogenic zone during kidney development. Here, the effect of the BET inhibitor JQ1 on renal development is evaluated. Inhibition of BET proteins via JQ1 leads to reduced growth of metanephric kidney cultures, loss of the nephron progenitor cell population, and premature and disturbed nephron differentiation. Gene expression of key nephron progenitor transcription factor Osr1 is downregulated after 24 h BET inhibition, while Lhx1 and Pax8 expression is increased. Mining of BRD4 ChIP-seq and gene expression data identify Osr1 as a key factor regulated by BRD4-controlled gene activation. Inhibition of BRD4 by BET inhibitor JQ1 leads to downregulation of Osr1, thereby causing a disturbance in the balance of nephron progenitor cell self-renewal and premature differentiation of the nephron, which ultimately leads to kidney hypoplasia and disturbed nephron development. This raises questions about the potential teratogenic effects of BET inhibitors for embryonic development. In summary, our work highlights the role of BET proteins for prenatal programming of nephrogenesis and identifies Osr1 as a potential target of BET proteins. Full article
(This article belongs to the Special Issue Glomerular Microenvironment: Cellular Stress in Chronic Kidney Disease)
►▼ Show Figures

Graphical abstract

12 pages, 2039 KiB  
Article
Glomerular Mesangial Cell pH Homeostasis Mediates Mineralocorticoid Receptor-Induced Cell Proliferation
by Michael Gekle and Sigrid Mildenberger
Biomedicines 2021, 9(9), 1117; https://doi.org/10.3390/biomedicines9091117 - 30 Aug 2021
Cited by 2 | Viewed by 1559
Abstract
Mineralocorticoids (e.g., aldosterone) support chronic inflammatory tissue damage, including glomerular mesangial injury leading to glomerulosclerosis. Furthermore, aldosterone leads to activation of the extracellular signal-regulated kinases (ERK1/2) in rat glomerular mesangial cells (GMC). Because ERK1/2 can affect cellular pH homeostasis via activation of Na [...] Read more.
Mineralocorticoids (e.g., aldosterone) support chronic inflammatory tissue damage, including glomerular mesangial injury leading to glomerulosclerosis. Furthermore, aldosterone leads to activation of the extracellular signal-regulated kinases (ERK1/2) in rat glomerular mesangial cells (GMC). Because ERK1/2 can affect cellular pH homeostasis via activation of Na+/H+-exchange (NHE) and the resulting cellular alkalinization may support proliferation, we tested the hypothesis that aldosterone affects pH homeostasis and thereby cell proliferation as well as collagen secretion also in primary rat GMC. Cytoplasmic pH and calcium were assessed by single-cell fluorescence ratio imaging, using the dyes BCECF or FURA2, respectively. Proliferation was determined by cell counting, thymidine incorporation and collagen secretion by collagenase-sensitive proline incorporation and ERK1/2-phosphorylation by Western blot. Nanomolar aldosterone induces a rapid cytosolic alkalinization which is prevented by NHE inhibition (10 µmol/L EIPA) and by blockade of the mineralocorticoid receptor (100 nmol/L spironolactone). pH changes were not affected by inhibition of HCO3− transporters and were not dependent on HCO3−. Aldosterone enhanced ERK1/2 phosphorylation and inhibition of ERK1/2-phosphorylation (10 µmol/L U0126) prevented aldosterone-induced alkalinization. Furthermore, aldosterone induced proliferation of GMC and collagen secretion, both of which were prevented by U0126 and EIPA. Cytosolic calcium was not involved in this aldosterone action. In conclusion, our data show that aldosterone can induce GMC proliferation via a MR and ERK1/2-mediated activation of NHE with subsequent cytosolic alkalinization. GMC proliferation leads to glomerular hypercellularity and dysfunction. This effect presents a possible mechanism contributing to mineralocorticoid receptor-induced pathogenesis of glomerular mesangial injury during chronic kidney disease. Full article
(This article belongs to the Special Issue Glomerular Microenvironment: Cellular Stress in Chronic Kidney Disease)
►▼ Show Figures

Figure 1

18 pages, 2566 KiB  
Article
Activated Alpha 2-Macroglobulin Is a Novel Mediator of Mesangial Cell Profibrotic Signaling in Diabetic Kidney Disease
by Jackie Trink, Renzhong Li, Yaseelan Palarasah, Stéphan Troyanov, Thomas E. Andersen, Johannes J. Sidelmann, Mark D. Inman, Salvatore V. Pizzo, Bo Gao and Joan C. Krepinsky
Biomedicines 2021, 9(9), 1112; https://doi.org/10.3390/biomedicines9091112 - 30 Aug 2021
Cited by 4 | Viewed by 2630
Abstract
Diabetic kidney disease (DKD) is caused by the overproduction of extracellular matrix proteins (ECM) by glomerular mesangial cells (MCs). We previously showed that high glucose (HG) induces cell surface translocation of GRP78 (csGRP78), mediating PI3K/Akt activation and downstream ECM production. Activated alpha 2-macroglobulin [...] Read more.
Diabetic kidney disease (DKD) is caused by the overproduction of extracellular matrix proteins (ECM) by glomerular mesangial cells (MCs). We previously showed that high glucose (HG) induces cell surface translocation of GRP78 (csGRP78), mediating PI3K/Akt activation and downstream ECM production. Activated alpha 2-macroglobulin (α2M*) is a ligand known to initiate this signaling cascade. Importantly, increased α2M was observed in diabetic patients’ serum, saliva, and glomeruli. Primary MCs were used to assess HG responses. The role of α2M* was assessed using siRNA, a neutralizing antibody and inhibitory peptide. Kidneys from type 1 diabetic Akita and CD1 mice and human DKD patients were stained for α2M/α2M*. α2M transcript and protein were significantly increased with HG in vitro and in vivo in diabetic kidneys. A similar increase in α2M* was seen in media and kidneys, where it localized to the mesangium. No appreciable α2M* was seen in normal kidneys. Knockdown or neutralization of α2M/α2M* inhibited HG-induced profibrotic signaling (Akt activation) and matrix/cytokine upregulation (collagen IV, fibronectin, CTGF, and TGFβ1). In patients with established DKD, urinary α2M* and TGFβ1 levels were correlated. These data reveal an important role for α2M* in the pathogenesis of DKD and support further investigation as a potential novel therapeutic target. Full article
(This article belongs to the Special Issue Glomerular Microenvironment: Cellular Stress in Chronic Kidney Disease)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

16 pages, 5731 KiB  
Review
Translational Approach to the Protective Effect of Bilirubin in Diabetic Kidney Disease
by Annalisa Bianco, Claudio Tiribelli and Cristina Bellarosa
Biomedicines 2022, 10(3), 696; https://doi.org/10.3390/biomedicines10030696 - 17 Mar 2022
Cited by 8 | Viewed by 6646
Abstract
Bilirubin has been regarded as a powerful endogenous antioxidant and anti-inflammatory molecule, able to act on cellular pathways as a hormone. Diabetic kidney disease (DKD) is a common chronic complication of diabetes, and it is the leading cause of end-stage renal disease. Here, [...] Read more.
Bilirubin has been regarded as a powerful endogenous antioxidant and anti-inflammatory molecule, able to act on cellular pathways as a hormone. Diabetic kidney disease (DKD) is a common chronic complication of diabetes, and it is the leading cause of end-stage renal disease. Here, we will review the clinical and molecular features of mild hyperbilirubinemia in DKD. The pathogenesis of DKD involves oxidative stress, inflammation, fibrosis, and apoptosis. Serum bilirubin levels are positively correlated with the levels of the antioxidative enzymes as superoxide dismutase, catalase, and glutathione peroxidase, while it is inversely correlated with C-reactive protein, TNF-α, interleukin (IL)-2, IL-6, and IL-10 release in diabetic kidney disease. Bilirubin downregulates NADPH oxidase, reduces the induction of pro-fibrotic factor HIF-1α expression, cleaved caspase-3, and cleaved PARP induction showing lower DNA fragmentation. Recent experimental and clinical studies have demonstrated its effects in the development and progression of renal diseases, pointing out that only very mild elevations of bilirubin concentrations result in real clinical benefits. Future controlled studies are needed to explore the precise role of bilirubin in the pathogenesis of DKD and to understand if the use of serum bilirubin levels as a marker of progression or therapeutic target in DKD is feasible and realistic. Full article
(This article belongs to the Special Issue Glomerular Microenvironment: Cellular Stress in Chronic Kidney Disease)
►▼ Show Figures

Figure 1

33 pages, 2855 KiB  
Review
Glomerular Biomechanical Stress and Lipid Mediators during Cellular Changes Leading to Chronic Kidney Disease
by Mukut Sharma, Vikas Singh, Ram Sharma, Arnav Koul, Ellen T. McCarthy, Virginia J. Savin, Trupti Joshi and Tarak Srivastava
Biomedicines 2022, 10(2), 407; https://doi.org/10.3390/biomedicines10020407 - 9 Feb 2022
Cited by 4 | Viewed by 3814
Abstract
Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical [...] Read more.
Hyperfiltration is an important underlying cause of glomerular dysfunction associated with several systemic and intrinsic glomerular conditions leading to chronic kidney disease (CKD). These include obesity, diabetes, hypertension, focal segmental glomerulosclerosis (FSGS), congenital abnormalities and reduced renal mass (low nephron number). Hyperfiltration-associated biomechanical forces directly impact the cell membrane, generating tensile and fluid flow shear stresses in multiple segments of the nephron. Ongoing research suggests these biomechanical forces as the initial mediators of hyperfiltration-induced deterioration of podocyte structure and function leading to their detachment and irreplaceable loss from the glomerular filtration barrier. Membrane lipid-derived polyunsaturated fatty acids (PUFA) and their metabolites are potent transducers of biomechanical stress from the cell surface to intracellular compartments. Omega-6 and ω-3 long-chain PUFA from membrane phospholipids generate many versatile and autacoid oxylipins that modulate pro-inflammatory as well as anti-inflammatory autocrine and paracrine signaling. We advance the idea that lipid signaling molecules, related enzymes, metabolites and receptors are not just mediators of cellular stress but also potential targets for developing novel interventions. With the growing emphasis on lifestyle changes for wellness, dietary fatty acids are potential adjunct-therapeutics to minimize/treat hyperfiltration-induced progressive glomerular damage and CKD. Full article
(This article belongs to the Special Issue Glomerular Microenvironment: Cellular Stress in Chronic Kidney Disease)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-5
Back to TopTop