Poulsom R, Kurkinen M, Prockop D J, Boot-Handford R P
Jefferson Institute of Molecular Medicine, Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
J Biol Chem. 1988 Jul 25;263(21):10072-6.
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.
在用链脲佐菌素诱导雄性CDF大鼠患糖尿病2天至28周后，检测了编码基底膜两种成分（IV型胶原α1链和层粘连蛋白B1链）的mRNA的稳态水平。在对照大鼠和糖尿病大鼠中，IV型胶原α1链的mRNA浓度/微克RNA随年龄显著下降。糖尿病2周和11周后，糖尿病组水平显著低于对照组。然而，28周后，与对照动物的水平无显著差异。用醛糖还原酶抑制剂Statil（350毫克/千克饮食）治疗对照大鼠和糖尿病大鼠，不影响IV型胶原α1链的mRNA水平。与IV型胶原α1链的mRNA浓度持续下降相反，糖尿病诱导后11至28周，层粘连蛋白B1链的mRNA水平增加了两倍。这种增加是由于对照大鼠衰老使层粘连蛋白B1 mRNA水平降低了约50%。用Statil治疗对层粘连蛋白B1 mRNA水平无影响。在对照大鼠中，层粘连蛋白B1:α1（IV）胶原的mRNA水平之比随年龄无变化。19周龄时平均比值为0.97±0.10，36周龄时为1.0±0.10。在糖尿病大鼠中，该比值从19周龄时的0.85±0.11显著增加到36周龄时的3.2±1.2。层粘连蛋白B1的mRNA丰度增加，提示层粘连蛋白合成增加可能导致链脲佐菌素诱导的糖尿病大鼠肾基底膜增厚和功能异常。
