Doi T, Striker L J, Kimata K, Peten E P, Yamada Y, Striker G E
Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1991 May 1;173(5):1287-90. doi: 10.1084/jem.173.5.1287.
Mice transgenic for growth hormone (GH) develop progressive glomerulosclerosis. The compositions of kidney extracellular matrix (ECM) and ECM mRNA were examined. The glomerulosclerotic areas in GH mice contained types I and IV collagen, laminin, and basement membrane heparan sulfate proteoglycan (HSPG), which increased with age. The type IV collagen, laminin B2, and HSPG mRNA levels in GH mice, measured by a solution hybridization RNase protection assay, were increased over normal littermates. These findings suggest that the accumulation of ECM components in the glomeruli of GH mice is regulated at the transcriptional level and that glomerulosclerosis is, in part, due to the excess production of ECM rather than simply a reduction in its turnover. The glomerular lesions in GH mice resemble diabetic nephropathy and may allow further dissection of the molecular basis of certain forms of glomerulosclerosis.
生长激素（GH）转基因小鼠会发生进行性肾小球硬化。对肾脏细胞外基质（ECM）的组成和ECM mRNA进行了检测。GH小鼠的肾小球硬化区域含有I型和IV型胶原、层粘连蛋白以及基底膜硫酸乙酰肝素蛋白聚糖（HSPG），且这些成分会随着年龄增长而增加。通过溶液杂交核糖核酸酶保护试验测定，GH小鼠的IV型胶原、层粘连蛋白B2和HSPG mRNA水平高于正常同窝小鼠。这些发现表明，GH小鼠肾小球中ECM成分的积累在转录水平受到调控，并且肾小球硬化部分是由于ECM的过量产生，而非仅仅是其周转减少所致。GH小鼠的肾小球病变类似于糖尿病肾病，可能有助于进一步剖析某些形式肾小球硬化的分子基础。
