After 4 weeks, we saw a modest increase in the development of mesangial matrix expansion in db uNX + Ang-II mice compared to the db UNX, but lower than the extent of the injury seen in db RAS mice.
After 4 weeks, db UNX developed mesangial matrix expansion that was significantly greater than that observed in db sham or db Ang-II mice, but less than in the contralateral db RAS kidney.
In striking contrast, the contralateral kidney of db RAS mice developed glomerular mesangial matrix expansion that was significantly greater than the contralateral kidney of WT RAS or db sham, as assessed in PAS-stained sections and de novo glomerular fibronectin deposition.
Mesangial matrix expansion consistently was far more extensive than in age-matched db sham mice, and was associated with de novo glomerular fibronectin expression.
Reduction of blood pressure was effective in reducing mesangial matrix expansion, fibronectin expression, interstitial fibrosis, and tubular atrophy in the contralateral kidney of db RAS mice.
Despite similar level of systolic blood pressure, the contralateral kidney of db RAS mice developed chronic renal injury characterized by development of mesangial matrix expansion, interstitial fibrosis, tubular atrophy, and interstitial inflammation, as opposed to the contralateral kidneys in a number of other strains of non-diabetic mice subjected to RAS [ 5, 16, 26].
However, as shown before, db/db mice with unilateral nephrectomy did develop greater glomerular mesangial matrix expansion than age-matched db/db mice with two kidneys [ 8, 32], although its extent was less than that of db RAS mice.
Few approaches exist to enumerate such database derivative structures, for example the 'metabolic in silico network expansion DB (MINE)' [23].
The db/db mice show many similarities to human diabetic nephropathy, including elevated glucose levels, glomerular hypertrophy, mesangial matrix expansion and albuminuria [44], [45].
Furthermore, treatment with anti TGFβ antibody has been shown to reduce or prevent hypertrophy and extracellular matrix expansion in both strptozotocin-induced diabetic mice [61], and db/db mice [62].
