Increased steady-state levels of laminin B1 mRNA in kidneys of long-term streptozotocin-diabetic rats. No effect of an aldose reductase inhibitor.
The steady-state levels of mRNAs coding for two components of basement membranes, the alpha 1 chain of type IV collagen and the B1 chain of laminin, were measured in the kidneys of male CDF rats following the induction of diabetes with streptozotocin for periods of between 2 days and 28 weeks. The concentration of mRNA for the alpha 1 chain of type IV collagen/microgram of RNA decreased markedly with age in control and diabetic rats. The diabetic level was significantly lower than control after 2 and 11 weeks of diabetes. After 28 weeks, however, there was no significant difference from the levels in control animals. Treatment of control and diabetic rats with the aldose reductase inhibitor Statil (350 mg/kg diet) did not affect the levels of the mRNA for the alpha 1 chain of type IV collagen. In contrast to the continuous decline in the concentration of mRNA for the alpha 1 chain of type IV collagen, the level of mRNA for the B1 chain of laminin increased two-fold between 11 and 28 weeks after induction of diabetes. This increase occurred as aging of control rats reduced the level of laminin B1 mRNA by approximately 50%. Treatment with Statil had no effect on laminin B1 mRNA levels. In control rats there was no change in the ratio of the levels of mRNAs for laminin B1: alpha 1 (IV) collagen with age. The mean ratio was 0.97 +/- 0.10 at 19 weeks and 1.0 +/- 0.10 at 36 weeks of age. In diabetic rats there was a marked increase in the ratio from 0.85 +/- 0.11 at 19 weeks to 3.2 +/- 1.2 at 36 weeks of age. The increased abundance of mRNA for laminin B1 raises the possibility that increased synthesis of laminin contributes to the thickening and abnormal function of renal basement membranes in streptozotocin-diabetic rats.
Poulsom
R
R
Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Kurkinen
M
M
Prockop
D J
DJ
Boot-Handford
R P
RP
D000375:Aging; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003094:Collagen / Q000235:genetics; D004247:DNA / Q000235:genetics; D004262:DNA Restriction Enzymes; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D007700:Kinetics; D007797:Laminin / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007797:Laminin; D010793:Phthalazines; D011724:Pyridazines; D012333:RNA, Messenger; C042829:ponalrestat; D003094:Collagen; D004247:DNA; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; D004262:DNA Restriction Enzymes