Abstract
Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic abnormalities of the diabetic milieu act in concert, perhaps via the common effector path of oxidative stress and development of reactive oxygen species, to promote podocyte damage. There is loss of nephrin from the slit diaphragm, increased synthesis of some of the components of the glomerular basement membrane, activation of pro-apoptotic and hypertrophic pathways, loss of the α3β1integrin and increased secretion of VEGF. These changes interact to lead to increased permeability, accumulation of abnormal extracellular matrix, apoptosis, foot process detachment and podocyte loss. The foot processes of the remaining podocytes hypertrophy and widen, with reduced filtration slit width. The end result is increasing proteinuria, basement membrane thickening and accumulation of mesangial matrix and declining renal function. Some currently used therapies, such as tight glucose control and inhibition of the renin angiotensin system, ameliorate these changes and prevent podocyte loss. Statins may also have a specific podocyte protective role. Other potential therapies include inhibitors of glycation, antioxidants, and inhibitors of growth factor and signalling pathways.
Keywords: basal cell membrane, Nephrin, p38 MAPK signalling, Angiotensin II, VEGF receptor 1
Current Pharmaceutical Design
Title: The Podocyte: a Potential Therapeutic Target in Diabetic Nephropathy?
Volume: 13 Issue: 26
Author(s): Sally M. Marshall
Affiliation:
Keywords: basal cell membrane, Nephrin, p38 MAPK signalling, Angiotensin II, VEGF receptor 1
Abstract: Over the last five years, much work has underlined the important role of the podocyte in the development of diabetic nephropathy. The metabolic and haemodynamic abnormalities of the diabetic milieu act in concert, perhaps via the common effector path of oxidative stress and development of reactive oxygen species, to promote podocyte damage. There is loss of nephrin from the slit diaphragm, increased synthesis of some of the components of the glomerular basement membrane, activation of pro-apoptotic and hypertrophic pathways, loss of the α3β1integrin and increased secretion of VEGF. These changes interact to lead to increased permeability, accumulation of abnormal extracellular matrix, apoptosis, foot process detachment and podocyte loss. The foot processes of the remaining podocytes hypertrophy and widen, with reduced filtration slit width. The end result is increasing proteinuria, basement membrane thickening and accumulation of mesangial matrix and declining renal function. Some currently used therapies, such as tight glucose control and inhibition of the renin angiotensin system, ameliorate these changes and prevent podocyte loss. Statins may also have a specific podocyte protective role. Other potential therapies include inhibitors of glycation, antioxidants, and inhibitors of growth factor and signalling pathways.
Export Options
About this article
Cite this article as:
Marshall M. Sally, The Podocyte: a Potential Therapeutic Target in Diabetic Nephropathy?, Current Pharmaceutical Design 2007; 13 (26) . https://dx.doi.org/10.2174/138161207781662957
DOI https://dx.doi.org/10.2174/138161207781662957 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
A2A Adenosine Receptor and its Modulators: Overview on a Druggable GPCR and on Structure-Activity Relationship Analysis and Binding Requirements of Agonists and Antagonists
Current Pharmaceutical Design Pyridoxamine, an Inhibitor of Advanced Glycation End Product (AGE) Formation Ameliorates Insulin Resistance in Obese, Type 2 Diabetic Mice
Protein & Peptide Letters Editorial (Thematic Issue: Combination Therapy of Vascular Diseases and Fangjiomics: When West Meets East in the Era of Phenomics)
Current Vascular Pharmacology The Prothrombotic State in Hypertension and the Effects of Antihypertensive Treatment
Current Pharmaceutical Design Vascular, Oxidative, and Synaptosomal Abnormalities During Aging and the Progression of Type 2 Diabetes
Current Neurovascular Research Diagnosis of Pathogens Using DNA Microarray
Recent Patents on Biotechnology Insights into the Regulation of Renal Hemodynamic Function in Diabetic Mellitus
Current Diabetes Reviews Demystifying the ACE Polymorphism: From Genetics to Biology
Current Pharmaceutical Design Novel Therapeutics for Diabetic Micro- and Macrovascular Complications
Current Medicinal Chemistry Antiplatelet Treatment in Peripheral Arterial Disease: The Role of Novel Antiplatelet Agents
Current Pharmaceutical Design Non-histone Methylation of SET7/9 and its Biological Functions
Recent Patents on Anti-Cancer Drug Discovery Angiotensin-Converting Enzyme - New Insights into Structure, Biological Significance and Prospects for Domain-Selective Inhibitors
Current Enzyme Inhibition The Journey From Metabolic Profiling to Biomarkers: The Potential of NMR Spectroscopy Based Metabolomics in Neurodegenerative Disease Research
Current Metabolomics Antioxidant and Antiinflammatory Activities of Curcumin on Diabetes Mellitus and its Complications
Current Pharmaceutical Design Geriatric Psychopharmacology in Acute Settings
Current Psychopharmacology Optimization of Cardiac Metabolism in Diabetes Mellitus
Current Pharmaceutical Design Medications not Intended for Treatment of Dyslipidemias and with a Variable Effect on Lipids
Current Pharmaceutical Design Kinins as Therapeutic Agents in Cardiovascular and Renal Diseases
Current Pharmaceutical Design Endothelial Progenitor Cells and Vascular Biology in Diabetes Mellitus: Current Knowledge and Future Perspectives
Current Diabetes Reviews Polymorphisms of the Aldose Reductase Gene and Susceptibility to Diabetic Microvascular Complications
Current Medicinal Chemistry