Overexpression of klotho protein modulates uninephrectomy-induced compensatory renal hypertrophy by suppressing IGF-I signals
Overexpression of klotho protein modulates uninephrectomy-induced compensatory renal hypertrophy by suppressing IGF-I signals
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DOI：
10.1016/j.bbrc.2011.02.089
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发表时间：
2011-04-01
影响因子：
3.1
通讯作者：
Kashihara, Naoki
中科院分区：
文献类型：
--
作者：
Nagasu, Hajime;Satoh, Minoru;Kashihara, Naoki
klotho基因在肾脏的远曲小管中高度表达，而其编码的蛋白具有许多生理和病理生理肾脏作用。我们研究了klotho蛋白对klotho转基因（KLTG）小鼠肾切除术后生理性代偿性肾肥大的影响。与野生型小鼠相比，KLTG小鼠的肾脏肥大受到抑制，这与klotho蛋白对胰岛素生长因子-1（IGF-1）信号传导的抑制有关。在体外，在用klotho质粒转染的人近端肾小管细胞中，IGF-1信号传导受到抑制。我们的数据表明，klotho通过抑制IGF-1信号通路调节肾切除术后的代偿性肾肥大，表明klotho蛋白在肾脏中的新生理作用。(C)2011 Elsevier Inc. All rights reserved.
The klotho gene is highly expressed in the distal convoluted tubule of the kidney, while its encoded protein has many physiological and pathophysiological renal roles. We investigated the effect of klotho protein on physiological compensatory renal hypertrophy after nephrectomy in klotho transgenic (KLTG) mice. Renal hypertrophy was suppressed in KLTG mice compared with wild-type mice, and this was associated with suppression of insulin growth factor-1 (IGF-1) signaling by klotho protein. In vitro, IGF-1 signaling was suppressed in human proximal tubular cells transfected with the klotho plasmid. Our data suggest that klotho modulates compensatory renal hypertrophy after nephrectomy via suppression of the IGF-1 signaling pathway, indicating a novel physiological role for klotho protein in the kidney. (C) 2011 Elsevier Inc. All rights reserved.