Effect of prostaglandin E(2) and hyaluronan on mesangial cell proliferation - A potential contribution to glomerular hypercellularity in diabetes
Effect of prostaglandin E(2) and hyaluronan on mesangial cell proliferation - A potential contribution to glomerular hypercellularity in diabetes
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DOI：
10.2337/diabetes.45.1.44
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发表时间：
1996-01-01
期刊：
影响因子：
7.7
通讯作者：
Dunlop, ME
中科院分区：
文献类型：
--
作者：
Mahadevan, P;Larkins, RG;Dunlop, ME
系膜细胞增殖是几种形式的人类和实验性肾小球病变的特征，包括糖尿病。非硫化糖胺聚糖透明质酸参与细胞周围基质组装的调节，在某些细胞类型中是有丝分裂原。我们以前已经证明，透明质酸在肾小球中的产生是以葡萄糖和前列腺素依赖的方式增加的。我们研究了糖尿病以及添加透明质酸和前列腺素E(2)(PGE(2))对富含系膜细胞的肾小球核心制剂摄取[H-3]胸腺嘧啶核苷的影响。与非糖尿病对照组相比，链脲佐菌素诱导的糖尿病大鼠肾小球核心制剂的[H-3]胸腺嘧啶核苷摄取显著增加(P<；0.001)。在两个实验组的肾小球核心，透明质酸(10(-12)~10(-8)mol/L)可增加[H-3]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，当在传代早期保持在培养中时，对升高的葡萄糖(5.6-25 mmol/L)以及添加透明质酸和前列腺素E(2)的反应是[H-3]胸腺嘧啶核苷摄取增加。我们认为前列腺素和透明质酸的产生对糖尿病高血糖环境的反应可能是系膜细胞增多的原因之一。
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 E(2) (PGE(2)) on the uptake of [H-3]thymidine by glomerular core preparations enriched in mesangial cells. When compared with nondiabetic controls, it was shown that [H-3]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 , (10(-12) to 10(-8) mol/l) increased the uptake of [H-3]thymidine. Further, mesangial cells from nondiabetic control glomerular cores, when maintained in culture in early passage, responded with increased [H-3]thymidine uptake to raised glucose (5.6-25 mmol/l) and to added hyaluronan and PGE(2). We propose that prostaglandin and hyaluronan production in response to a raised glucose environment in diabetes can contribute to mesangial hypercellularity.