Rethinking glomerular basement membrane thickening in diabetic nephropathy: adaptive or pathogenic?
Autor: | Caroline B. Marshall |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Physiology Kidney Glomerulus urologic and male genital diseases Article Podocyte Diabetic nephropathy 03 medical and health sciences Glomerular Basement Membrane Medicine Animals Humans Diabetic Nephropathies business.industry urogenital system Podocytes Glomerular basement membrane Glomerulosclerosis medicine.disease female genital diseases and pregnancy complications 030104 developmental biology medicine.anatomical_structure Immunology Albuminuria Glomerular Filtration Barrier Kidney Failure Chronic Microalbuminuria medicine.symptom business Kidney disease |
Popis: | Diabetic nephropathy (DN) is the leading cause of chronic kidney disease in the United States and is a major cause of cardiovascular disease and death. DN develops insidiously over a span of years before clinical manifestations, including microalbuminuria and declining glomerular filtration rate (GFR), are evident. During the clinically silent period, structural lesions develop, including glomerular basement membrane (GBM) thickening, mesangial expansion, and glomerulosclerosis. Once microalbuminuria is clinically apparent, structural lesions are often considerably advanced, and GFR decline may then proceed rapidly toward end-stage kidney disease. Given the current lack of sensitive biomarkers for detecting early DN, a shift in focus toward examining the cellular and molecular basis for the earliest structural change in DN, i.e., GBM thickening, may be warranted. Observed within one to two years following the onset of diabetes, GBM thickening precedes clinically evident albuminuria. In the mature glomerulus, the podocyte is likely key in modifying the GBM, synthesizing and assembling matrix components, both in physiological and pathological states. Podocytes also secrete matrix metalloproteinases, crucial mediators in extracellular matrix turnover. Studies have shown that the critical podocyte-GBM interface is disrupted in the diabetic milieu. Just as healthy podocytes are essential for maintaining the normal GBM structure and function, injured podocytes likely have a fundamental role in upsetting the balance between the GBM's synthetic and degradative pathways. This article will explore the biological significance of GBM thickening in DN by reviewing what is known about the GBM's formation, its maintenance during health, and its disruption in DN. |
Databáze: | OpenAIRE |
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