Brittain Alison L, Kopchick John J
Edison Biotechnology Institute and Heritage College of Osteopathic Medicine, Ohio University, Konneker Research Center 206A, Athens, OH 45701, USA.
Growth Horm IGF Res. 2019 Oct-Dec;48-49:1-4. doi: 10.1016/j.ghir.2019.07.001. Epub 2019 Jul 16.
Despite decades of study on the contribution of growth hormone (GH) to the development of kidney disease, there remains the question of the relative contribution of elevated levels of GH to kidney damage in humans, particularly in diabetic nephropathy occurring in type 1 patients. In this study, we reviewed several publicly available datasets to examine transcription of twelve genes associated with the GH/IGF1 axis in several types of human and rodent kidney diseases. Our analyses revealed downregulation of renal GHR and IGF1 gene expression in several different chronic human kidney diseases, including diabetic nephropathy, with general upregulation of IGFBP6 in the same tissues and diseases. These findings were generally supported by a review of studies in rodent models. In healthy and diseased human kidneys, increased GHR gene expression was associated with increases in glomerular filtration rate (GFR) and decreases in serum creatinine. IGFBP6 gene expression demonstrated the opposite clinical correlation. Our results suggest the kidney may exhibit GH insensitivity due to low GHR gene expression during most chronic kidney diseases.
尽管数十年来一直在研究生长激素（GH）对肾脏疾病发展的影响，但对于GH水平升高对人类肾脏损伤，尤其是1型糖尿病患者发生的糖尿病肾病的相对影响，仍然存在疑问。在本研究中，我们查阅了几个公开可用的数据集，以检查与GH/IGF1轴相关的12个基因在几种人类和啮齿动物肾脏疾病中的转录情况。我们的分析显示，在包括糖尿病肾病在内的几种不同慢性人类肾脏疾病中，肾脏GHR和IGF1基因表达下调，而在相同组织和疾病中IGFBP6普遍上调。这些发现总体上得到了啮齿动物模型研究综述的支持。在健康和患病的人类肾脏中，GHR基因表达增加与肾小球滤过率（GFR）升高和血清肌酐降低相关。IGFBP6基因表达表现出相反的临床相关性。我们的结果表明，在大多数慢性肾脏疾病中，由于GHR基因表达较低，肾脏可能表现出对GH不敏感。
