In a rat model of subtotal nephrectomy, increased procollagen alpha1(IV) mRNA levels correlate with matrix expansion (basement membrane thickening) rather than tubular hypertrophy.
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Animal data link procollagen alpha1(IV) to tubular matrix expansion; hypothesis-generating for human CKD mechanisms.
The relationships between tubular hypertrophy/hyperplasia, procollagen alpha1(IV) mRNA levels, and the development of tubular basement membrane thickening were studied in male Sprague-Dawley rats subjected to subtotal renal ablation and sacrificed 2 or 15 days later. Tubular hypertrophy and hyperplasia were demonstrable at 2 days, however no increment in procollagen alpha1 (IV) mRNA levels was discerned at that time, demonstrating a dissociation between mRNA levels for classical type IV collagen and tubular enlargement. At 15 days, tubular procollagen alpha1(IV) mRNA levels did increase approximately 2-fold (p < 0.002), localizing predominantly in proximal tubules in the deep cortex and outer medullary stripe. At this time point, there was still no significant correlation to tubular enlargement, but there was a significant correlation to tubular basement membrane thickening (r = 0.89, p < 0.01). These studies demonstrated that an increase in mRNA for classical type IV collagen is not required for the development of hypertrophy, and that the increment is a better marker for matrix expansion than it is for hypertrophy.
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Adler et al. (1998) studied this question.
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