Cell volume regulatory mechanisms in progression of renal disease.
One of the striking morphological features of renal failure is an increase of cell volume. This review explores the role of cell volume regulatory mechanisms in the pathophysiology of progressive renal disease. The case is made that TGF-beta, a major cytokine involved in the development of progressive renal failure, upregulates the transcription of the serum and glucocorticoid-dependent kinase hSGK1, involved in cell volume regulation. Excessive extracellular glucose concentrations stimulate TGF-beta1 expression and thus similarly enhance hSGK1-transcription. The kinase stimulates two mechanisms important for cell volume regulation, i.e. the renal epithelial Na+ channel ENaC and the thick ascending limb Na+,K+,2Cl- cotransporter BSC1. On the one hand, stimulation of renal tubular transport leads to renal retention of Na+, which favours the development of hypertension. On the other, the increase of cell volume stimulates protein synthesis and inhibits protein degradation, contributing to the enhanced net formation and deposition of matrix proteins. At later stages, the increase of cell volume may be reversed to atrophy, and cell death may lead to loss of functional tissue. In conclusion, progressive renal disease is paralleled by deranged cell volume regulatory mechanisms.
Wärntges
S
S
Department for Physiology, University of Tübingen, Germany.
Gröne
H J
HJ
Capasso
G
G
Lang
F
F
D030201:Activin Receptors, Type I / Q000096:biosynthesis* / Q000235:genetics; D002462:Cell Membrane / Q000378:metabolism; D048429:Cell Size / Q000502:physiology; D018450:Disease Progression; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins; D007674:Kidney Diseases / Q000503:physiopathology*; D007684:Kidney Tubules / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins; D009994:Osmolar Concentration; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D011506:Proteins / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
D030201:Activin Receptors, Type I; D005947:Glucose; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta; D028021:Sodium-Potassium-Chloride Symporters; D000099184:Serum-Glucocorticoid Regulated Kinases