Mahadevan P, Larkins R G, Fraser J R, Dunlop M E
Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Diabetes. 1996 Jan;45(1):44-50. doi: 10.2337/diab.45.1.44.
Proliferation of mesangial cells is a feature of several forms of human and experimental glomerulopathy, including that seen in diabetes. The nonsulfated glycosaminoglycan hyaluronan participates in the regulation of pericellular matrix assembly and is a mitogen in some cell types. We have shown previously that hyaluronan production is increased in the glomerulus in a glucose- and prostaglandin-dependent manner. We have investigated the effect of diabetes and of addition of hyaluronan and prostaglandin E2 (PGE2) on the uptake of [3H]thymidine by glomerular core preparations enriched in mesangial cells. When compared with nondiabetic controls, it was shown that [3H]thymidine uptake was significantly increased in glomerular core preparations from streptozotocin-induced diabetic rats (to 169 +/- 5%, P < 0.001). In glomerular cores from both experimental groups, hyaluronan (50-250 ng/ml) or PGE2 (10(-12) to 10(-8) mol/l) increased the uptake of [3H]thymidine. Further, mesangial cells from nondiabetic control glomerular cores, when maintained in culture in early passage, responded with increased [3H]thymidine uptake to raised glucose (5.6-25 mmol/l) and to added hyaluronan and PGE2. We propose that prostaglandin and hyaluronan production in response to a raised glucose environment in diabetes can contribute to mesangial hypercellularity.
系膜细胞增殖是多种人类和实验性肾小球病的特征，包括糖尿病相关的肾小球病。非硫酸化糖胺聚糖透明质酸参与细胞周围基质组装的调节，并且在某些细胞类型中是一种促有丝分裂原。我们之前已经表明，透明质酸的产生在肾小球中以葡萄糖和前列腺素依赖的方式增加。我们研究了糖尿病以及添加透明质酸和前列腺素E2（PGE2）对富含系膜细胞的肾小球核心制剂摄取[3H]胸腺嘧啶核苷的影响。与非糖尿病对照组相比，结果显示链脲佐菌素诱导的糖尿病大鼠的肾小球核心制剂中[3H]胸腺嘧啶核苷摄取显著增加（至169±5%，P<0.001）。在两个实验组的肾小球核心中，透明质酸（50 - 250 ng/ml）或PGE2（10^(-12)至10^(-8) mol/l）均增加了[3H]胸腺嘧啶核苷的摄取。此外，来自非糖尿病对照肾小球核心的系膜细胞在早期传代培养时，对升高的葡萄糖（5.6 - 25 mmol/l）以及添加的透明质酸和PGE2反应为[3H]胸腺嘧啶核苷摄取增加。我们认为，糖尿病中对升高的葡萄糖环境作出反应而产生的前列腺素和透明质酸可能导致系膜细胞增多。
