Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria

Jing Ning, Zhicong Xiang, Chongxiang Xiong, Qin Zhou, Xin Wang, Hequn Zou Department of Nephropathy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaCorrespondence: Hequn ZouDepartment of Nephropathy, The Third Affiliated Hospital o...

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Autores principales:	Ning J, Xiang Z, Xiong C, Zhou Q, Wang X, Zou H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	diabetic kidney disease urinary extracellular vesicles biomarker alpha1-antitrypsin inflammation tubular epithelial cell Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/c74f0ac68c84454b953ef64b721403e9
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spelling	oai:doaj.org-article:c74f0ac68c84454b953ef64b721403e92021-12-02T09:33:37ZAlpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria1178-7007https://doaj.org/article/c74f0ac68c84454b953ef64b721403e92020-06-01T00:00:00Zhttps://www.dovepress.com/alpha1-antitrypsin-in-urinary-extracellular-vesicles-a-potential-bioma-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Jing Ning, Zhicong Xiang, Chongxiang Xiong, Qin Zhou, Xin Wang, Hequn Zou Department of Nephropathy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaCorrespondence: Hequn ZouDepartment of Nephropathy, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria.Patients and Methods: UEVs were isolated from the urine of healthy subjects, pre-diabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α 1-AT) by Western blot. To explore the function of α 1-AT in the inflammatory process leading to DKD, we silenced the expression of α 1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR.Results: There was no expression of α 1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α 1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α 1-AT in tubular epithelial cells was inhibited under high glucose stimulation.Conclusion: Our results suggest that α 1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.Keywords: diabetic kidney disease, urinary extracellular vesicles, biomarker, alpha1-antitrypsin, inflammation, tubular epithelial cellNing JXiang ZXiong CZhou QWang XZou HDove Medical Pressarticlediabetic kidney diseaseurinary extracellular vesiclesbiomarkeralpha1-antitrypsininflammationtubular epithelial cellSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 2037-2048 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	diabetic kidney disease urinary extracellular vesicles biomarker alpha1-antitrypsin inflammation tubular epithelial cell Specialties of internal medicine RC581-951
spellingShingle	diabetic kidney disease urinary extracellular vesicles biomarker alpha1-antitrypsin inflammation tubular epithelial cell Specialties of internal medicine RC581-951 Ning J Xiang Z Xiong C Zhou Q Wang X Zou H Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria
description	Jing Ning, Zhicong Xiang, Chongxiang Xiong, Qin Zhou, Xin Wang, Hequn Zou Department of Nephropathy, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, People’s Republic of ChinaCorrespondence: Hequn ZouDepartment of Nephropathy, The Third Affiliated Hospital of Southern Medical University, 183 Zhongshan West Avenue, Tianhe District, Guangzhou 510630, People’s Republic of ChinaTel +86 20 6278 4391Email hequnzou@hotmail.comPurpose: Diabetic kidney disease (DKD), which is related to inflammation and immune response, is the primary vascular complication of diabetes mellitus and also the leading etiology of end-stage renal disease. Urinary extracellular vesicles (UEVs) are an attractive source for biomarker detection as they involve molecular constituents derived from their parental sections of the nephron. In this study, we aimed to search for a potential biomarker in UEVs for the early diagnosis and prediction of DKD, especially before the emergence of microalbuminuria.Patients and Methods: UEVs were isolated from the urine of healthy subjects, pre-diabetic, and diabetic patients with varying degrees of kidney damage by ultracentrifugation, and the extracted UEVs were used to measure alpha1-antitrypsin (α 1-AT) by Western blot. To explore the function of α 1-AT in the inflammatory process leading to DKD, we silenced the expression of α 1-AT in renal tubular epithelial cells using cell transfection techniques to assess the differential expression of the inflammatory factors such as MCP-1 and TNF-α using qRT-PCR.Results: There was no expression of α 1-AT in the UEVs of either healthy or pre-diabetic subjects. Its expression was significantly increased in the UEVs of diabetic patients with normoalbuminuria (prior to microalbuminuria), which was more sensitive and more stable than other renal indexes to predict DKD. Additionally, the expression of α 1-AT in UEVs was gradually upregulated with the aggravation of DKD and the decline of renal function. In vitro, the mRNA expression of MCP-1 and TNF-α was significantly decreased when the generation of α 1-AT in tubular epithelial cells was inhibited under high glucose stimulation.Conclusion: Our results suggest that α 1-AT derived from UEVs, especially in diabetic patients with normoalbuminuria, might serve as a potential noninvasive biomarker for diagnosis of DKD early in the development of the disease and may predict the future decline of renal function.Keywords: diabetic kidney disease, urinary extracellular vesicles, biomarker, alpha1-antitrypsin, inflammation, tubular epithelial cell
format	article
author	Ning J Xiang Z Xiong C Zhou Q Wang X Zou H
author_facet	Ning J Xiang Z Xiong C Zhou Q Wang X Zou H
author_sort	Ning J
title	Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria
title_short	Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria
title_full	Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria
title_fullStr	Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria
title_full_unstemmed	Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria
title_sort	alpha1-antitrypsin in urinary extracellular vesicles: a potential biomarker of diabetic kidney disease prior to microalbuminuria
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/c74f0ac68c84454b953ef64b721403e9
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Alpha1-Antitrypsin in Urinary Extracellular Vesicles: A Potential Biomarker of Diabetic Kidney Disease Prior to Microalbuminuria

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