Depts. of Medicine and Pharmacology, University of California San Diego & VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 May;300(5):R1009-22. doi: 10.1152/ajpregu.00809.2010. Epub 2011 Jan 12.
Diabetic nephropathy is a leading cause of end-stage renal disease. A better understanding of the molecular mechanism involved in the early changes of the diabetic kidney may permit the development of new strategies to prevent diabetic nephropathy. This review focuses on the proximal tubule in the early diabetic kidney, particularly on its exposure and response to high glucose levels, albuminuria, and other factors in the diabetic glomerular filtrate, the hyperreabsorption of glucose, the unique molecular signature of the tubular growth phenotype, including aspects of senescence, and the resulting cellular and functional consequences. The latter includes the local release of proinflammatory chemokines and changes in proximal tubular salt and fluid reabsorption, which form the basis for the strong tubular control of glomerular filtration in the early diabetic kidney, including glomerular hyperfiltration and odd responses like the salt paradox. Importantly, these early proximal tubular changes can set the stage for oxidative stress, inflammation, hypoxia, and tubulointerstitial fibrosis, and thereby for the progression of diabetic renal disease.
糖尿病肾病是终末期肾病的主要原因。更好地了解糖尿病肾脏早期变化所涉及的分子机制，可能有助于开发新的策略来预防糖尿病肾病。这篇综述重点介绍了早期糖尿病肾脏中的近端小管，特别是其对高血糖、白蛋白尿和糖尿病肾小球滤液中其他因素的暴露和反应、葡萄糖的过度重吸收、管状生长表型的独特分子特征，包括衰老方面，以及由此产生的细胞和功能后果。后者包括促炎趋化因子的局部释放和近端管状盐和液体重吸收的变化，这为早期糖尿病肾脏中的肾小球滤过的强烈管状控制奠定了基础，包括肾小球高滤过和盐悖论等奇怪反应。重要的是，这些早期的近端小管变化可能为氧化应激、炎症、缺氧和肾小管间质纤维化，以及糖尿病肾病的进展创造条件。
