Mechanical strain of glomerular mesangial cells in the pathogenesis of glomerulosclerosis: clinical implications.
Due to their elasticity, glomeruli will undergo excessive expansion and repetitive cycles of distension contraction under conditions of impaired glomerular pressure autoregulation and systemic arterial hypertension. These alterations in glomerular volume are associated with mesangial cell stretch which in turn stimulates the synthesis and deposition of ECM with eventual mesangial expansion and glomerulosclerosis. Hyperactivity of growth factors with prosclerotic activity is an important component in the translation of cellular mechanical strain into the abnormal metabolism of ECM components. Although mesangial cell mechanical strain is expected to occur in both remnant glomeruli and in glomeruli of diabetic kidneys, quantitatively different factors will determine the resultant metabolic consequences. In remnant glomeruli, the mechanical stretch is intense, being accounted for largely by the marked glomerular hypertrophy and increased glomerular compliance. In diabetic glomeruli, however, the mechanical stretch is less prominent but its effect on ECM synthesis is markedly aggravated by the presence of hyperglycaemia. There are presently no methods clinically available to diminish the prosclerotic action of growth factors at the glomerular level. In addition, there are no effective means to specifically improve glomerular pressure autoregulation. Therefore, current therapies must be aimed at decreasing systemic arterial pressure, blocking angiotensin II action and reducing glomerular hypertrophy. While there are effective drugs for the treatment of hypertension and for angiotensin II inhibition, protein restriction is the only measure available to diminish glomerular hypertrophy. Finally, in diabetes correction of systemic and glomerular hypertension should be coupled with strict glycaemic control to correct both glomerular autoregulation and increased ECM deposition.
Cortes
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P
Riser
B L
BL
Yee
J
J
Narins
R G
RG
D001696:Biomechanical Phenomena; D005109:Extracellular Matrix / Q000378:metabolism; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D011312:Pressure; D012598:Sclerosis; D013314:Stress, Mechanical