Transforming growth factor-beta regulates production of proteoglycans by mesangial cells.
Transforming growth factor-beta regulates production of proteoglycans by mesangial cells.
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发表时间：
1990
影响因子：
19.6
通讯作者：
W. A. Border;Seiya Okuda;R. Languino;E. Ruoslahti
中科院分区：
文献类型：
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作者：
W. A. Border;Seiya Okuda;R. Languino;E. Ruoslahti
肾小球细胞外基质的积累是大多数形式的进行性肾小球疾病的显着特征。由于某些生长因子可能在细胞外基质的产生中发挥作用，我们研究了转化生长因子-β (TGF-β)、白细胞介素 1、血小板衍生生长因子和肿瘤坏死因子对培养的大鼠系膜细胞产生细胞外基质成分的影响。在对照实验中，我们发现系膜细胞产生两种不同的蛋白多糖，被鉴定为小软骨素/硫酸皮肤素蛋白多糖双糖链 (PG I) 和核心蛋白聚糖 (PG II)，通过显示它们在 SDS-PAGE 上的迁移率在被软骨素酶 ABC 消化后发生变化，并且它们与针对来自人双糖链和核心蛋白聚糖核心蛋白序列的合成肽产生的抗体发生反应。暴露于 TGF-β 48 小时可刺激双糖链蛋白聚糖和核心蛋白聚糖条带增加 8 至 10 倍，并诱导结构变化（检测为电泳迁移率的变化）。 TGF-β 并未明显影响系膜细胞产生其他基质蛋白。测试的其他生长因子对这些细胞产生蛋白聚糖或其他细胞外基质成分没有类似的影响。我们的结果表明，TGF-β 在生长因子中对系膜细胞蛋白多糖产生的调节作用是独一无二的。肾小球损伤期间 TGF-β 的释放或激活可能介导细胞外基质中蛋白聚糖的积累，并使肾脏易于发生肾小球硬化。
Accumulation of glomerular extracellular matrix is a prominent feature of most forms of progressive glomerular disease. Since some growth factors may play a role in extracellular matrix production, we examined the effects of transforming growth factor-beta (TGF-beta), interleukin 1, platelet derived growth factor, and tumor necrosis factor on the production of extracellular matrix components by cultured rat mesangial cells. In control experiments we found that mesangial cells produced two distinct proteoglycans identified as the small chondroitin/dermatan sulfate proteoglycans biglycan (PG I) and decorin (PG II) by showing that their mobility on SDS-PAGE changed upon digestion by chondroitinase ABC, and that they reacted with antibodies raised against synthetic peptides from the core protein sequence of human biglycan and decorin. Exposure to TGF-beta for 48 hours stimulated an 8- to 10-fold increase in the biglycan and decorin bands, and induced a structural change detected as a shift in electrophoretic mobility. TGF-beta did not demonstrably affect the production of other matrix proteins by the mesangial cells. The other growth factors tested had no comparable effect on the production of proteoglycans or other extracellular matrix components by these cells. Our results show that TGF-beta is unique among growth factors in its regulatory effects on mesangial cell proteoglycan production. The release or activation of TGF-beta during glomerular injury could mediate the accumulation of proteoglycans in the extracellular matrix and predispose the kidney to development of glomerulosclerosis.