Increased expression of decorin in experimental hydronephrosis
Increased expression of decorin in experimental hydronephrosis
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DOI：
10.1038/ki.1997.156
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发表时间：
1997-04-01
影响因子：
19.6
通讯作者：
Ricardo, SD
中科院分区：
文献类型：
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作者：
Diamond, JR;Levinson, M;Ricardo, SD
转化生长因子-β1是大鼠单侧输尿管梗阻(UUO)模型肾小管间质纤维化的潜在介质。核心蛋白聚糖是一种由核心蛋白和硫酸软骨素侧链组成的蛋白质，能够灭活转化生长因子-β。由于转化生长因子-β在实验性肾小球肾炎中强烈诱导核心蛋白聚糖的合成，我们的目的是研究在大鼠UUO模型中核心蛋白核心蛋白的表达变化是否有效。在输尿管结扎后24小时，梗阻肾(OBK)与对侧未梗阻肾(CUK)相比，肾皮质Decorin mRNA表达开始升高(2.5倍)，在OBK标本中，在48(2.3倍)、96(2.2倍)和168(1.9倍)小时仍高于对侧(1.9倍)。UUO前11天全身X射线照射可显著降低UUO后24小时和96小时的核心蛋白核心蛋白基因表达。免疫标记显示，Decorin仅在UUO后各时间点的CUK标本的血管外膜有明显表达。相反，输尿管结扎后96小时，肾小球周间质和肾小管周围间质中有核心蛋白核心蛋白的表达，而输尿管结扎后168小时，肾小管间质中核心蛋白粘附素的表达变得更加强烈和弥漫。在Western分析中，在UUO后96小时和168小时，OBK和CUK标本中Decorin蛋白的表达有非常显著的增加。在UUO后48小时和96小时，OBK肾皮质中的活性转化生长因子-β1水平分别是CUK的1.9倍和3.6倍。综上所述，我们证明了UUO后，OBK的肾皮质中Decorin的mRNA和蛋白的表达上调，而CUK的肾皮质中的表达与活跃的转化生长因子-β1水平和巨噬细胞的浸润呈时间上的平行关系。我们推测，在这个模型中，TI纤维化的发展可能只与转化生长因子-β对核心蛋白的生理性诱导有关，并且可能需要药物水平来通过抑制转化生长因子-β来延缓或防止瘢痕形成。
Transforming growth factor (TGF)-beta 1 is a potential mediator of tubulointerstitial (TI) fibrosis in the rat unilateral ureteral obstruction (UUO) model. Decorin is a protein composed of a core protein and a chondroitin sulfate side chain and is capable of inactivating TGF-beta. Since TGF-beta strongly induces the synthesis of decorin in experimental glomerulonephritis, it was our intent to investigate whether altered decorin expression is operant in the rat UUO model. Renal cortical decorin mRNA levels initially became elevated (2.5-fold) in obstructed kidney (OBK) versus contralateral unobstructed kidney (CUK) 24 hours post-UUO and remained greater in the OBK specimens at 48 (2.3-fold), 96 (2.2-fold), and 168 (1.9-fold) hours post-ureteral ligation. Whole-body X-irradiation 11 days prior to UUO significantly reduced decorin mRNA at 24 and 96 hours post-UUO. On immunolabeling, decorin was only evident in the adventitia of blood vessels in CUK specimens at any time point after UUO. In contrast, OBK specimens initially demonstrated periglomerular and peritubular interstitial localization of decorin at 96 hours post-ureteral ligation, which became even more intense and diffuse in the tubulointerstitium at 168 hours post-UUO. On Western analysis, there were highly significant increases in decorin protein expression in the OBK versus the CUK specimens al 96 and 168 hours post-UUO. Levels of active TGF-beta 1 in the renal cortex of OBK were 1.9- and 3.6-fold higher than CUK at 48 and 96 hours post-UUO. In summary, we demonstrated that post-UUO, decorin mRNA and protein expression is up-regulated in the renal cortex of OBK, but not CUK, specimens in a temporal parallel with active TGF-beta 1 levels and macrophage infiltration. We postulate that the development of TI fibrosis in this model may be related to only a physiologic induction of decorin by TGF-beta, and that pharmacologic levels may be required to retard or prevent scarring via TGF-beta inhibition.