Severely reduced production of Klotho in human chronic renal failure kidney
Severely reduced production of Klotho in human chronic renal failure kidney
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DOI：
10.1006/bbrc.2000.4226
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发表时间：
2001-02-02
影响因子：
3.1
通讯作者：
Nabeshima, Y
中科院分区：
文献类型：
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作者：
Koh, N;Fujimori, T;Nabeshima, Y
我们最近发现了一种新的基因，称为klotho (hl)，它参与了一种类似人类衰老的小鼠综合症的发展。小鼠hi基因表达缺陷导致多种疾病，包括动脉硬化、骨质疏松、异位钙化和皮肤萎缩，并导致寿命缩短和不孕。慢性肾功能衰竭（CRF）患者会出现多种并发症，这些并发症与在hi突变小鼠中观察到的表型相似。此外，hi基因主要在肾和脑中表达。以上证据提示CRF患者并发症可能与Klotho功能有关。为了探讨上述可能性，我们检查了10例临床或组织学诊断的CRF病例的肾脏。采用RNase保护法检测kl基因的表达水平。采用Western blot和免疫组化方法检测Klotho蛋白的表达。在所有CRF肾脏中，hi mRNA表达水平均显著降低。此外，在所有CRF肾脏中，Klotho蛋白的产生也严重减少。这些结果提示，CRF患者hi基因表达的降低可能是CRF患者多重并发症恶化过程的基础。(C) 2001学术出版社。
We recently identified a novel gene, termed klotho (hl) that is involved in the development of a syndrome in mice resembling human aging. A defect of the hi gene expression in mice leads to multiple disorders including arteriosclerosis, osteoporosis, ectopic calcification, and skin atrophy together with short lifespan and infertility. Patients with chronic renal failure (CRF), develop multiple complications that are reminiscent of phenotypes observed in hi mutant mice. Furthermore, the hi gene is mainly expressed in kidney and brain. These evidences above suggest the possible involvement of Klotho function in the complications arising in CRF patients. To investigate the above possibility, we examined the kidneys of 10 clinically or histologically diagnosed CRF cases. The level of kl gene expression was measured by utilizing RNase protection assay. The expression of Klotho protein was assayed by utilizing Western blot analysis and by immunohistochemistry. The levels of hi mRNA expression were greatly reduced in all CRF kidneys. Moreover, the production of Klotho protein was also severely reduced in all CRF kidneys. These results suggest that the decrease in hi gene expression in CRF patients may underlie the deteriorating process of multiple complications in the CRF patients. (C) 2001 Academic Press.