Simonson M S
Department of Medicine, Case Western Reserve University, Cleveland, OH 44106.
Curr Opin Nephrol Hypertens. 1994 Jan;3(1):73-85. doi: 10.1097/00041552-199401000-00011.
Endothelins are paracrine or autocrine peptides that regulate diverse aspects of renal function. In addition to their potent vasoconstrictor activity, recent evidence suggests that endothelin-1 is a growth factor for renal cells. Different forms of renal injury markedly upregulate endothelin-1 secretion, which is postulated to contribute to compensatory renal growth. Similar roles have been hypothesized for other vasoactive peptides, such as angiotensin II and arginine vasopressin. New information has recently emerged regarding pathways of mitogenic signaling linking activation of endothelin receptors to changes in gene expression. ETA receptor subtypes activate downstream effectors, such as protein kinase C, protein tyrosine kinases of the src gene family, and mitogen-activated protein kinases. These cytosolic effectors in turn lead to altered programs of gene expression by activating, among others, AP-1 and serum response factor transcription factors. In addition, recent studies in organisms amenable to genetic analysis, such as Drosophila, Dictyostelium, and yeast, are providing important clues to effector mechanisms employed by vasoactive peptide receptors in higher organisms. Information on the molecular mechanisms for mitogenic signaling by endothelin receptors might be used to gain insight into the pathogenesis of compensatory renal growth and the development of novel therapeutic strategies.
内皮素是调节肾功能多个方面的旁分泌或自分泌肽。除了其强大的血管收缩活性外，最近的证据表明内皮素-1是肾细胞的生长因子。不同形式的肾损伤会显著上调内皮素-1的分泌，推测这有助于肾的代偿性生长。对于其他血管活性肽，如血管紧张素II和精氨酸加压素，也有类似作用的假设。最近出现了关于将内皮素受体激活与基因表达变化联系起来的促有丝分裂信号传导途径的新信息。ETA受体亚型激活下游效应器，如蛋白激酶C、src基因家族的蛋白酪氨酸激酶和丝裂原活化蛋白激酶。这些胞质效应器进而通过激活AP-1和血清反应因子转录因子等，导致基因表达程序改变。此外，最近在果蝇、盘基网柄菌和酵母等适合进行遗传分析的生物体中的研究，为高等生物中血管活性肽受体所采用的效应器机制提供了重要线索。关于内皮素受体促有丝分裂信号传导分子机制的信息，可能有助于深入了解肾代偿性生长的发病机制以及开发新的治疗策略。
