The Latest Molecular Research on Renal Disease

Dear Colleagues,

Renal disease encompasses a broad range of conditions such as glomerulonephritis, ischemic nephropathy, and diabetic nephropathy and remains a significant health issue. While the clinical management of kidney diseases has advanced over the last few years, molecular research continues to provide insights into pathogenesis, diagnosis, and potential therapies.

This Special Issue will cover all aspects of molecular research related to acute and chronic kidney injury, including both animal models and clinical studies in patients.

We invite the submission of scientific papers, including reviews as well as original investigations, within this research field. Potential topics include molecular mechanisms, novel genetic insights, stem cell and regeneration therapy, microRNAs, epigenetics, and novel therapeutic targets.

1. Molecular Mechanisms behind Kidney Injury

Recent molecular research has significantly enhanced our understanding of the cellular and molecular pathways involved in kidney injury. A key focus has been the role of inflammation, fibrosis, and oxidative stress.

• Inflammation: The inflammatory response is central to the development and progression of renal diseases. The activation of immune cells, such as T-cells and macrophages, contributes to tubulointerstitial fibrosis. A variety of cytokines and growth factors (e.g., TNF-alpha, IL-6) are upregulated, leading to further injury to renal structures.
• Fibrosis: Renal fibrosis is considered the final common pathway in many forms of kidney disease, leading to irreversible damage and the loss of kidney function. The role of myofibroblasts in the progression of fibrosis has been widely studied, with research focusing on signaling pathways such as TGF-β and Wnt/β-catenin that regulate fibrotic processes.
• Oxidative Stress: Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) and antioxidant defenses, is a central factor in kidney injury. Studies have elucidated the molecular pathways by which oxidative stress induces renal cell damage and promotes inflammation and fibrosis.

2. Genetic Insights into Renal Disease

A growing body of research has identified genetic variants linked to various kidney diseases. Genome-wide association studies (GWASs) have uncovered several genetic loci associated with CKD, offering insights into the molecular underpinnings of these diseases. These include variants in genes such as APOL1, UMOD, and NOS3, which have been associated with an increased risk of kidney disease.

• APOL1 Gene: The APOL1 gene has garnered significant attention due to its association with increased susceptibility to kidney diseases in individuals of African descent. Variants of APOL1 have been shown to confer risk for conditions like focal segmental glomerulosclerosis (FSGS) and HIV-associated nephropathy.
• UMOD Gene: Mutations in the UMOD gene, which encodes uromodulin, a protein expressed in the kidneys, are linked to medullary cystic kidney disease and CKD. Uromodulin has a protective role in the kidneys, and alterations in its expression can contribute to disease progression.
• NOS3 Gene: Variants in the NOS3 gene, which encodes endothelial nitric oxide synthase, have been implicated in hypertension-related kidney damage. Nitric oxide is important in regulating vascular tone and kidney perfusion, and its dysfunction may contribute to renal injury.

3. Renal Regeneration and Stem Cell Research

One exciting area of research in renal disease is the potential for renal regeneration through stem cell therapy. Recent advancements in the identification of renal progenitor cells and induced pluripotent stem cells (iPSCs) have opened up new avenues for therapeutic interventions.

• Renal Progenitor Cells: Studies have identified specific populations of cells within the kidney that have the potential to regenerate damaged renal tissue. Research is focusing on how these progenitor cells can be activated or transplanted to repair renal damage.
• iPSCs: Induced pluripotent stem cells (iPSCs) have been used to model renal diseases in vitro, enabling the study of disease mechanisms and drug testing. These cells can be differentiated into various renal cell types, offering a potential strategy for kidney repair and regeneration.

4. The Role of MicroRNAs and Epigenetics

MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are emerging as important regulators of kidney function and disease. Research has identified miRNAs that modulate key pathways involved in kidney fibrosis, inflammation, and apoptosis.

• miRNAs in Fibrosis: Several miRNAs, including miR-21 and miR-29, have been shown to be involved in the regulation of fibrosis by targeting genes that control extracellular matrix deposition and myofibroblast differentiation.
• Epigenetic Modifications: Epigenetic changes, such as DNA methylation and histone modifications, have been shown to play a role in the pathogenesis of kidney disease. These modifications can alter the expression of genes involved in renal injury and repair, and understanding these changes could lead to novel therapeutic approaches.

5. Emerging Therapeutic Targets

Molecular research on kidney diseases has paved the way for the development of novel therapeutic strategies aimed at specific molecular pathways.

• Anti-Fibrotic Agents: Targeting fibrotic pathways holds great promise for preventing or reversing kidney damage. Agents that inhibit TGF-β signaling or block the Wnt/β-catenin pathway are being explored in clinical trials.
• Gene Therapy: With the identification of specific genetic mutations responsible for kidney disease, gene therapy offers a potential route for addressing the root cause of genetic renal diseases. This could involve correcting defective genes or delivering therapeutic genes to the kidneys.
• Targeting Inflammation: Drugs that target inflammatory pathways, such as inhibitors of TNF-alpha, IL-6, or complement pathways, are being studied for their ability to reduce kidney injury and improve outcomes.

Dr. Niels Henrik Buus
Dr. Marco Eijken
Guest Editors

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• renal disease
• chronic kidney disease
• renal regeneration
• kidney injury