Molecular and Cellular Mechanisms of Kidney Diseases

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

Deadline for manuscript submissions: 31 October 2025 | Viewed by 1554

Special Issue Editors


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Guest Editor
Professor of Nephrology, Department of Nephrology, Faculty of Medicine, University of Thessaly, Larissa, Greece
Interests: chronic kidney disease; acute kidney injury; kidney transplantation; glomerular diseases; ischemia–reperfusion injury; glucose toxicity; immunology
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Guest Editor
Assistant Professor, Department of Nephrology, Faculty of Medicine, University of Thessaly, Larissa, Greece
Interests: chronic kidney disease; acute kidney injury; diabetic nephropathy; hypertension; glomerular diseases; ischemia–reperfusion injury

Special Issue Information

Dear Colleagues,

The global prevalence of chronic kidney disease (CKD) is estimated to exceed 10% and is on the rise, posing a significant challenge due to its detrimental effects on both quality of life and life expectancy. Concurrently, the incidence of acute kidney injury (AKI) remains high, particularly among hospitalized and critically ill patients, often resulting in poorer prognoses for these individuals.

Fortunately, extensive research over many years has led to the development of new diagnostic tools and therapeutic approaches for specific diseases contributing to CKD, especially various types of glomerulopathies, as well as strategies to decelerate CKD progression in general. Nevertheless, the residual risk remains high. Similar advancements have been made in the field of kidney transplantation; however, long-term kidney transplant survival has not significantly improved over the past decades. Efforts are also underway to facilitate earlier detection of AKI, although interventions targeting the molecular pathophysiology of AKI have not yet been widely implemented in clinical practice.

This Special Issue, titled "Molecular and Cellular Mechanisms of Kidney Diseases," invites authors to submit innovative reviews or original research articles on the mechanisms involved in the pathogenesis and complications of chronic kidney disease (CKD) and acute kidney injury (AKI). Additionally, we welcome translational articles that discuss the mechanisms of action of new or emerging therapies.

We look forward to receiving your contributions.

Dr. Theodoros Eleftheriadis
Dr. Maria Divani
Guest Editors

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Keywords

  • chronic kidney disease
  • acute kidney injury
  • kidney transplantation
  • glomerular diseases
  • ischemia–reperfusion injury
  • diabetic nephropathy

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Published Papers (1 paper)

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Research

16 pages, 3007 KiB  
Article
Modulators of Alpha-2 Macroglobulin Upregulation by High Glucose in Glomerular Mesangial Cells
by Jackie Trink, Renzhong Li, Bo Gao, Chao Lu and Joan C. Krepinsky
Biomolecules 2024, 14(11), 1444; https://doi.org/10.3390/biom14111444 - 13 Nov 2024
Viewed by 1107
Abstract
Up to 40% of patients with diabetes mellitus will develop diabetic kidney disease (DKD), characterized pathologically by the accumulation of extracellular matrix proteins, which leads to the loss of kidney function over time. Our previous studies showed that the pan-protease inhibitor alpha 2-macroglobulin [...] Read more.
Up to 40% of patients with diabetes mellitus will develop diabetic kidney disease (DKD), characterized pathologically by the accumulation of extracellular matrix proteins, which leads to the loss of kidney function over time. Our previous studies showed that the pan-protease inhibitor alpha 2-macroglobulin (A2M) is increased in DKD and is a critical regulator of the fibrotic response in glomerular mesangial cells (MC), an initial site of injury during DKD development. How A2M is regulated by high glucose (HG) has not yet been elucidated and is the focus of this investigation. Using serial deletions of the full A2M promoter, we identified the −405 bp region as HG-responsive in MC. Site-directed mutagenesis, siRNA, and ChIP studies showed that the transcription factor, nuclear factor of activated T cells 5 (NFAT5), regulated A2M promoter activity and protein expression in response to HG. Forkhead box P1 (FOXP1) served as a cooperative binding partner for NFAT5, required for A2M upregulation. Lastly, we showed that Smad3, known for its role in kidney fibrosis, regulated A2M promoter activity and protein production independently of HG. The importance of NFAT5, FOXP1, and Smad3 in A2M regulation was confirmed in ex vivo studies using isolated glomeruli. In conclusion, Smad3 is required for basal and HG-induced A2M expression, while NFAT5 and FOXP1 cooperatively regulate increased A2M transcription in response to HG. Inhibition of NFAT5/FOXP1 will be further evaluated as a potential therapeutic strategy to inhibit A2M production and attenuate profibrotic signaling in DKD. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Kidney Diseases)
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