Special Issue "Molecular Mechanisms of Kidney Injury and Repair"

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 30 November 2019.

Special Issue Editor

Prof. Grazyna Nowak
E-Mail Website
Guest Editor
Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, United States
Interests: Ischemia- and Toxicant-Induced Acute Kidney Injury; Bioenergetics; Mitochondrial Dysfunction; Protein Phosphorylation; Proteomics; Protein Kinases; Cell Injury; Mechanisms of Cell Death

Special Issue Information

Dear Colleagues,

Kidney disease remains a global public health concern because of high morbidity and mortality, and significant healthcare costs are associated with this disease. Diabetes and hypertension are the major causes of chronic kidney disease, which gradually leads to reduced quality of life and well-being. Ischemia, hypoxia, exposure to nephrotoxic compounds, and infections are the leading causes of acute kidney injury, which is encountered in a variety of clinical settings and is characterized by a rapid decline in kidney function and the failure to regulate fluid, electrolyte, and acid–base balance. The kidney has a remarkable ability to repair and regenerate its morphology and functions. However, inflammatory response and incomplete or maladaptive repair of the kidney after acute injury can lead to fibrosis and chronic kidney disease. Thus, acute kidney injury is a major risk factor for chronic and end-stage renal diseases. The therapeutic strategies used to treat acute kidney injury are still insufficient and dialysis remains the major therapeutic intervention to improve kidney recovery and patient survival.

Acute injury and chronic disease of the kidney in humans are multifactorial events. The pathogenesis of acute kidney injury is associated with a series of cellular responses to the initial insult that involve different cellular compartments, pathways and mechanisms, and a large variety of molecular targets. These responses involve protein unfolding and loss of function, DNA damage, cell cycle and growth arrest, mitochondrial dysfunction and changes in the energy metabolism, endoplasmic reticulum and oxidative stress, alterations in gene transcription and translation, disruption of biosignaling pathways, innate immune response, increased autophagy, and cell death. If the injury and stress are not too severe, repair processes are activated to replace lost cells, restore cellular metabolism and functions, and recover kidney functions. If the insult is prolonged or too severe, cellular stress and tissue dysfunction continue and the inflammatory cells are recruited to the kidney, initiating a sequelae of events leading to inflammation, fibrosis, and eventually the progressive loss of function characteristic of chronic kidney disease. Progress made in understanding these complex pathophysiological mechanisms and cellular events resulted in the development of several new biomarkers to diagnose acute kidney injury and its progression to chronic kidney disease. Hopefully, the continuation of studies into these areas will lead to the development of therapeutic approaches that prevent and/or treat acute kidney injury, or block the progression to chronic and end-stage renal diseases.

This Special Issue of Biomelecules seeks manuscripts that 1) elucidate cellular and molecular mechanisms and pathways mediating kidney injury and recovery, 2) identify molecular targets that are effective in preventing cell injury or promoting cell repair after injury, and 3) describe new animal models that could better represent these mechanisms in human kidenys. We encourage scientists working in this area of research to submit research articles, communications, or critical reviews that synthesize the current research literature and discuss emerging directions. Thus, these studies will contribute to the development of therapeutic interventions that target the mechanisms of kidney injury and repair.

Prof. Grazyna Nowak
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 papers will be 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. Biomolecules 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 1200 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

  • Pathogenesis of acute and chronic kidney injury
  • Ischemic and nephrotoxic kidney injury
  • Glomerular/interstitial/vascular damage
  • Tubular necrosis, necroptosis, apoptosis, pyroptosis, and ferroptosis
  • Inflammatory signals and fibrosis
  • Bioenergetics, mitochondrial damage and biogenesis
  • Autophagy and mitophagy
  • Transcription factors in kidney injury
  • Receptors and signaling pathways
  • Cell cycle proteins
  • Biomarkers
  • Renal repair and regeneration
  • Cytoprotection and therapeutic intervention
  • In vivo models of kidney injury

Published Papers (4 papers)

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Research

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Open AccessArticle
All-Trans Retinoic Acid Attenuates Fibrotic Processes by Downregulating TGF-β1/Smad3 in Early Diabetic Nephropathy
Biomolecules 2019, 9(10), 525; https://doi.org/10.3390/biom9100525 - 25 Sep 2019
Abstract
Diabetic nephropathy (DN) involves damage associated to hyperglycemia and oxidative stress. Renal fibrosis is a major pathologic feature of DN. The aim of this study was to evaluate anti-fibrogenic and renoprotective effects of all-trans retinoic acid (ATRA) in isolated glomeruli and proximal tubules [...] Read more.
Diabetic nephropathy (DN) involves damage associated to hyperglycemia and oxidative stress. Renal fibrosis is a major pathologic feature of DN. The aim of this study was to evaluate anti-fibrogenic and renoprotective effects of all-trans retinoic acid (ATRA) in isolated glomeruli and proximal tubules of diabetic rats. Diabetes was induced by single injection of streptozotocin (STZ, 60 mg/Kg). ATRA (1 mg/Kg) was administered daily by gavage, from days 3–21 after STZ injection. ATRA attenuated kidney injury through the reduction of proteinuria, renal hypertrophy, increase in natriuresis, as well as early markers of damage such as β2-microglobulin, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL). The following parameters increased: macrophage infiltration, localization of alpha-smooth muscle actin (αSMA)-positive cells in renal tissue, and pro-fibrotic proteins such as transforming growth factor-β (TGF-β1), laminin beta 1 (LAM-β1), and collagens IV and I. Remarkably, ATRA treatment ameliorated these alterations and attenuated expression and nuclear translocation of Smad3, with increment of glomerular and tubular Smad7. The diabetic condition decreased expression of retinoic acid receptor alpha (RAR-α) through phosphorylation in serine residues mediated by the activation of c-Jun N-terminal kinase (JNK). ATRA administration restored the expression of RAR-α and inhibited direct interactions of JNK/RAR-α. ATRA prevented fibrogenesis through down-regulation of TGF-β1/Smad3 signaling. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Kidney Injury and Repair)
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Open AccessArticle
Mechanisms of Fasting-Mediated Protection against Renal Injury and Fibrosis Development after Ischemic Acute Kidney Injury
Biomolecules 2019, 9(9), 404; https://doi.org/10.3390/biom9090404 - 22 Aug 2019
Abstract
Ischemia-reperfusion injury of the kidney may lead to renal fibrosis through a combination of several mechanisms. We recently demonstrated that fasting protects the rat kidney against oxidative stress and mitochondrial dysfunction in early acute kidney injury, and also against fibrosis development. Here we [...] Read more.
Ischemia-reperfusion injury of the kidney may lead to renal fibrosis through a combination of several mechanisms. We recently demonstrated that fasting protects the rat kidney against oxidative stress and mitochondrial dysfunction in early acute kidney injury, and also against fibrosis development. Here we show that preoperative fasting preserves redox status and mitochondrial homeostasis at the chronic phase of damage after severe ischemia. Also, the protective effect of fasting coincides with the suppression of inflammation and endoplasmic reticulum stress, as well as the down-regulation of the mechanistic target of rapamycin (mTOR) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in the fibrotic kidney. Our results demonstrate that fasting targets multiple pathophysiological mechanisms to prevent renal fibrosis and damage that results after renal ischemia-reperfusion injury. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Kidney Injury and Repair)
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Open AccessArticle
Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury
Biomolecules 2019, 9(8), 348; https://doi.org/10.3390/biom9080348 - 06 Aug 2019
Abstract
Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought [...] Read more.
Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN. However, their exact role in the pathophysiology of DN remains unclear. Here, we examined the effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high glucose conditions on naïve RPTCs in vitro. Our results showed significant increases in the levels of phosphorylated forms of 4E-binding protein 1 and ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2α (an ER stress marker), alpha smooth muscle actin (an EMT marker), and phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-β signaling). Together, our findings indicate that MPs activate key signaling pathways in RPTCs under high glucose conditions. Pharmacological interventions to inhibit shedding of MPs from RPTCs might serve as an effective strategy to prevent the progression of DN. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Kidney Injury and Repair)
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Review

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Open AccessReview
Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments
Biomolecules 2019, 9(4), 141; https://doi.org/10.3390/biom9040141 - 08 Apr 2019
Cited by 1
Abstract
Renal fibrosis is the common pathway for most forms of progressive renal disease. The Unilateral Ureteral Obstruction (UUO) model is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow. Furthermore, experimental [...] Read more.
Renal fibrosis is the common pathway for most forms of progressive renal disease. The Unilateral Ureteral Obstruction (UUO) model is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow. Furthermore, experimental UUO in rodents is believed to mimic human chronic obstructive nephropathy in an accelerated manner. Renal fibrosis is the common pathway for most forms of progressive renal disease. Removing the obstruction may not be sufficient to reverse fibrosis, so an accompanying treatment may be of benefit. In this review, we have done a revision on treatments shown to ameliorate fibrosis in the context of the UUO experimental model. The treatments inhibit the production of fibrotic and inflammatory proteins such as Transforming Growth Factor β1 (TGF-β1), Tumor Necrosis Factor α (TNF-α), collagen and fibronectin, Heat Shock Protein 47 (HSP47), suppress the proliferation of fibroblasts, prevent epithelial-to-mesenchymal transition, reduce oxidative stress, inhibit the action of the Nuclear Factor κB (NF-κB), reduce the phosphorylation of mothers against decapentaplegic homolog (SMAD) family members 2 and 3 (Smad2/3) or Mitogen-Activated Protein Kinases (MAPKs), inhibit the activation of the renin-angiotensin system. Summaries of the UUO experimental methods and alterations observed in the UUO experiments are included. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Kidney Injury and Repair)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Grazyna Nowak (Guest Editor), William J. Craigen and Judit Megyesi
University of Arkansas for Medical Sciences, USA
Baylor College of Medicine, USA
Medical University of South Carolina, USA

Lee Ann MacMillan-Crow
University of Arkansas for Medical Sciences, USA

 

 

 

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