Kolbe M, Kaufman J L, Friedman J, Dinerstein C, Mackenzie J W, Boyd C D
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903.
Connect Tissue Res. 1990;25(1):77-85. doi: 10.3109/03008209009009814.
The development of capillary basement membrane thickening has been linked to microvascular changes known to occur in tissues of patients with type II diabetes. Previous evidence has suggested that capillary basement membrane thickening is due to increased basement membrane synthesis. In this study, skin samples from 8 diabetic patients with confirmed capillary basement membrane thickening and 7 non-diabetic controls were used to assess steady state levels of mRNAs coding for several basement components including pro alpha 1(IV) collagen, laminin and fibronectin. Total RNA was extracted from abdominal skin samples and levels of mRNAs coding for the basement membrane components laminin, fibronectin and pro alpha 1(IV) collagen, a fibrillar collagenous protein, pro alpha 1(I) collagen and an intracellular polypeptide, gamma-actin, were determined by dot blot hybridization analysis. While there were no changes of steady state levels of pro alpha 1(I) collagen mRNA and laminin mRNA, a significant reduction was noted in the quantitative recovery of mRNA levels for pro alpha 1(IV) collagen, gamma-actin and fibronectin in total RNA isolated from the skin of diabetic patients. This reduction in levels of mRNAs coding for basement membrane components contrasts with pathological confirmation of an accumulation of endothelial capillary basement membrane in skin from diabetic patients and suggests that basement membrane thickening arises more as a consequence of reduced basement membrane degradation than elevated synthesis of basement membrane components.
毛细血管基底膜增厚的发展与已知发生在II型糖尿病患者组织中的微血管变化有关。先前的证据表明，毛细血管基底膜增厚是由于基底膜合成增加所致。在本研究中，使用了8例经证实有毛细血管基底膜增厚的糖尿病患者和7例非糖尿病对照者的皮肤样本，来评估编码几种基底成分的mRNA的稳态水平，这些成分包括α1（IV）前胶原、层粘连蛋白和纤连蛋白。从腹部皮肤样本中提取总RNA，并通过斑点印迹杂交分析确定编码基底膜成分层粘连蛋白、纤连蛋白和α1（IV）前胶原（一种纤维状胶原蛋白）、α1（I）前胶原和一种细胞内多肽γ-肌动蛋白的mRNA水平。虽然α1（I）前胶原mRNA和层粘连蛋白mRNA的稳态水平没有变化，但从糖尿病患者皮肤中分离的总RNA中，α1（IV）前胶原、γ-肌动蛋白和纤连蛋白的mRNA水平的定量回收率显著降低。编码基底膜成分的mRNA水平的这种降低与糖尿病患者皮肤中内皮毛细血管基底膜积累的病理证实形成对比，表明基底膜增厚更多是由于基底膜降解减少而非基底膜成分合成增加所致。
