Lina Wang1, Jie Lin2, Ting Yu3, Qianfei Zuo4, Bingbing Shen5, Huhai Zhang5, Baolian Liu5, Dongping Cai2, Hui Mao2, Hongwen Zhao6, Quanming Zou7, Bin Xiao8. 1. Department of Clinical and Military Laboratory Medicine, College of Medical Laboratory Science, Army Medical University, Chongqing 400038, China. 2. Department of Clinical Laboratory, The 904th Hospital of The People's Liberation Army, Wuxi 214044, China. 3. Department of Clinical Laboratory, The 89th Hospital of The People's Liberation Army, WeiFang 261000, China. 4. National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China. 5. Department of Kidney, Southwest Hospital, Army Medical University, Chongqing 400038, China. 6. Department of Kidney, Southwest Hospital, Army Medical University, Chongqing 400038, China. Electronic address: zhaohongwen@medmail.com.cn. 7. National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China. Electronic address: qmzoutmmu@yeah.net. 8. National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, China; College of Pharmacy, Chongqing Medical University, Chongqing 400016, China. Electronic address: binxiaotmmu@163.com.
Abstract
BACKGROUND: Although stable microRNAs (miRNAs) are present in human peripheral blood and have been considered as novel biomarkers for various diseases. But there is little research about miRNAs as biomarkers of mesangial proliferative glomerulonephritis (MsPGN). This study aimed to identify whether there exist disordered circulating miRNAs that can function as biomarkers for MsPGN disease activity. METHODS: The candidate miRNAs were validated in 70 MsPGN patients and 70 healthy controls by quantitative real-time PCR (RT-qPCR). The specificity and sensitivity of the miRNA panel was assessed by receiver operating characteristic (ROC) curves. In addition, the candidate miRNA levels were measured in the different MsPGN progression and in the membranous nephropathy (MN) patients and the hypothetical role of the candidate miRNA on mesangial cell proliferation was analysed. Situ hybridization was performed to examine the candidate miRNA levels in the glomerulus. RESULTS: These results showed that miR-106a-5p and miR-30a-5p were highly expressed in MsPGN patients compared with healthy controls and could discriminate MsPGN from healthy controls with an area under the ROC curve (AUC) of 0.93. In addition, the two miRNAs were not only higher in moderate and severe MsPGN patients, but could distinguish MsPGN from MN. We also observed a decreased expression in MsPGN regression group after treatment. Plasma miR-106a-5p level was positively correlated with estimated glomerular filtration rate (eGFR). Furthermore, the two miRNAs were highly expressed in MsPGN glomerulus and their overexpression could prompt mesangial cell proliferation. CONCLUSION: Plasma miR-30a-5p and miR-106a-5p can serve as novel and potential diagnostic biomarkers for MsPGN.
BACKGROUND: Although stable microRNAs (miRNAs) are present in human peripheral blood and have been considered as novel biomarkers for various diseases. But there is little research about miRNAs as biomarkers of mesangial proliferative glomerulonephritis (MsPGN). This study aimed to identify whether there exist disordered circulating miRNAs that can function as biomarkers for MsPGN disease activity. METHODS: The candidate miRNAs were validated in 70 MsPGN patients and 70 healthy controls by quantitative real-time PCR (RT-qPCR). The specificity and sensitivity of the miRNA panel was assessed by receiver operating characteristic (ROC) curves. In addition, the candidate miRNA levels were measured in the different MsPGN progression and in the membranous nephropathy (MN) patients and the hypothetical role of the candidate miRNA on mesangial cell proliferation was analysed. Situ hybridization was performed to examine the candidate miRNA levels in the glomerulus. RESULTS: These results showed that miR-106a-5p and miR-30a-5p were highly expressed in MsPGN patients compared with healthy controls and could discriminate MsPGN from healthy controls with an area under the ROC curve (AUC) of 0.93. In addition, the two miRNAs were not only higher in moderate and severe MsPGN patients, but could distinguish MsPGN from MN. We also observed a decreased expression in MsPGN regression group after treatment. Plasma miR-106a-5p level was positively correlated with estimated glomerular filtration rate (eGFR). Furthermore, the two miRNAs were highly expressed in MsPGN glomerulus and their overexpression could prompt mesangial cell proliferation. CONCLUSION: Plasma miR-30a-5p and miR-106a-5p can serve as novel and potential diagnostic biomarkers for MsPGN.