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| Aims: Angiotensin-converting enzyme-2 (ACE2) plays a critical role in regulation of renin-angiotensin system (RAS) and is important for the development of chronic kidney disease (CKD). ACE2 is highly expressed in tubular epithelial and glomerular cells. Urinary exosomes are microvesicles released by tubular epithelial cells and podocytes containing information of their originated cells. This study aimed to investigate expression of ACE2 mRNA in urinary exosome in different stages of CKD and to explore its correlation with renal function and histological changes. Methods: Urine samples were collected from 31 patients of chronic kidney disease（CKD） who underwent kidney biopsy and 7 controls. Urinary exosome was isolated with differential ultracentrifugation and ACE2 mRNA was detected by real-time RT-PCR on RNA isolated from urinary exosome. Results: The pellet microvesicles were positively stained with exosome marker, AQP2. The mRNA level of ACE2 showed no difference in kidney disease patients compared with controls. However, ACE2 mRNA was differently expressed in different stages of kidney disease (p=0.009 by Kruskal-Wallis test). In CKD patients with eGFR<90ml/min/1.73 m2 (n=18), ACE2 mRNA correlated with eGFR (r=-0.480, p=0.044), BUN (r=0.527, p=0.025) and score of glomerulosclerosis (r=-0.521, p=0.027). No correlation was found between ACE2 and score of tubulointerstitial fibrosis (TIF). Interestingly, in group of TIF<30%, ACE2 correlated positively with levels of glomerulosclerosis (r=0.668, p=0.007) while in group of TIF>30%, ACE2 correlated negatively with glomerulosclerosis (r=-0.663, p=0.007). In both groups, no correlation was found between eGFR and glomerulosclerosis.Conclusions: ACE2 mRNA could be readily detected in urinary exosome with different levels in different stages of CKD. It might be a novel biomarker for kidney disease reflecting the severity of glomerulosclerosis and renal function. In this paper………..(10 Points, Times New Roman) |
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| Keywords:chronic kidney diseaase, Angiotensin-converting enzyme-2; exosome; urine |
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