Takahashi Kazuhiro, Hirose Takuo, Mori Nobuyoshi, Morimoto Ryo, Kohzuki Masahiro, Imai Yutaka, Totsune Kazuhito
Department of Endocrinology and Applied Medical Science, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Peptides. 2009 Aug;30(8):1575-85. doi: 10.1016/j.peptides.2009.05.018. Epub 2009 May 27.
The incidence of chronic kidney disease, such as diabetic nephropathy, is increasing throughout the world. Many biologically active peptides play important roles in the kidney. The classical example is the renin-angiotensin system (RAS). Angiotensin II plays critical roles in the progression of chronic kidney disease through its vasoconstrictor action, stimulatory action on cell proliferation, and reactive oxygen-generating activity. A renin inhibitor, aliskiren, has recently been shown to be a clinically effective drug to reduce proteinuria in patients with diabetic nephropathy. (Pro)renin receptor, a specific receptor for renin and prorenin, was newly identified as a member of the RAS. When bound to prorenin, (pro)renin receptor activates the angiotensin I-generating activity of prorenin in the absence of cleavage of the prosegment, and directly stimulates the pathway of mitogen-activated protein kinase independently from the RAS. The kidney peptides that antagonize the intrarenal RAS may have renoprotective actions. Adrenomedullins, potent vasodilator peptides, have been shown to have renoprotective actions. On the other hand, urotensin II, a potent vasoconstrictor peptide, may promote the renal dysfunction in chronic kidney disease together with the renal RAS. Thus, in addition to the renin inhibitor and (pro)renin receptor, adrenomedullins and urotensin II may be novel targets to develop therapeutic strategies against chronic kidney disease.
诸如糖尿病肾病之类的慢性肾脏病的发病率在全球范围内正在上升。许多生物活性肽在肾脏中发挥着重要作用。经典的例子是肾素-血管紧张素系统（RAS）。血管紧张素II通过其血管收缩作用、对细胞增殖的刺激作用以及产生活性氧的活性，在慢性肾脏病的进展中起着关键作用。一种肾素抑制剂阿利吉仑，最近已被证明是一种临床上有效的药物，可减少糖尿病肾病患者的蛋白尿。（前体）肾素受体，一种肾素和前体肾素的特异性受体，最近被新确定为RAS的成员。当与前体肾素结合时，（前体）肾素受体在没有前肽裂解的情况下激活前体肾素产生血管紧张素I的活性，并独立于RAS直接刺激丝裂原活化蛋白激酶途径。拮抗肾内RAS的肾脏肽可能具有肾脏保护作用。肾上腺髓质素，一种强效血管舒张肽，已被证明具有肾脏保护作用。另一方面，尾加压素II，一种强效血管收缩肽，可能与肾脏RAS一起促进慢性肾脏病中的肾功能障碍。因此，除了肾素抑制剂和（前体）肾素受体之外，肾上腺髓质素和尾加压素II可能是开发针对慢性肾脏病治疗策略的新靶点。
