Type IV collagen antigens in serum of diabetic rats: a marker for basement membrane collagen biosynthesis

The nature of type IV collagen antigens in the serum of streptozotocin diabetic rats was studied using radioimmunoassays for the N-terminal (7S-collagen) and C-terminal domain of type IV collagen. Type IV collagen antigen crossreacting with antibodies to the C-terminal domain was elevated from 32.0±5.36 ng/ml (n=10) in serum of normal rats to 94.9±24.5 ng/ml (n=10,P<0.0001) in serum of streptozotocin diabetic rats and could be normalized to 40.1±8.30 ng/ml (n=18) by insulin treatment. Molecular sieve chromatography of serum demonstrated a high molecular weight fraction containing the C-terminal and N-terminal domains and smaller material containing only the N-terminal domain. Degradation of the high molecular weight material by collagenase indicates that it consists of intact collagen type IV. Its relative proportion increased from 42% to 54% 4 weeks after diabetes induction. Together with unaltered clearance rates of 7S collagen in normal and diabetic rats, the data suggest that the increase of collagen type IV antigens in diabetic states reflects increased synthesis of collagen type IV.