The important clinical problems of
diabetic nephropathy are both
proteinuria and decrease of renal function. Pathological analysis showed decrease of GFR was correlated to degree of mesangial expansion but not thickening of GBM nor the other findings in human type 1
diabetic nephropathy. From the perspective in renal dysfunction, mesangial matrix expansion was crucial for
diabetic nephropathy. However, there was no difference of mesangial expansion between normal and microalbuminuria stage in type 1 and 2
diabetes mellitus (DM). On the other hand, microalbuminuria definitely shows a key related factor for cardiovascular events, but it does not indicate a clear interaction for glomerulosclerosis. We need to search a new
clinical marker for renal injury. We have first shown that Smad1 is a
transcription factor for alpha1 and 2 of type 4
collagen (Col4), which is a major component of glomerulosclerosis. We have also identified Smad1 is a critical responsible molecule for developing glomerulosclerosis in rat
diabetic nephropathy. We have found the good correlation between glomerulosclerosis and urinary Smad1 but not between glomerulosclerosis and urine
albumin. These data suggests that urine Smad1 is a promising
clinical marker for underlying glomerular damages in early stage
diabetic nephropathy. The study also implicates that
angiotensin II (AngII)-Src-Smad1 signaling pathway has played a key role for development of
diabetic nephropathy. These suggest that it is necessary to clarify the whole mechanism related to Smad1 to identify the pathogenesis of
diabetic nephropathy.