| Objective: To judge the relationship between the expression level of serum exosomes microRNA-1207-5p and clinical indicators of patients with diabetic kidney disease(DKD)in different stages and different risk progression groups and explore the clinical value of measuring the risk of renal function progression in DKD patients.At the same time,the current research status of microRNA-1207-5p is analyzed,and the previous research combined with database prediction summarizes its ceRNA regulatory network to provide a basis for its future research.Methods:1.According to the inclusion and exclusion criteria,51 patients with type 2diabetes(T2DM)and DKD admitted to the Department of Endocrinology and Metabolism and the Department of Nephrology,the Second Hospital of Lanzhou University from December 2021 to February 2023 were selected,and 11 healthy people without any disease were selected as the control group.First,the cases were divided into 1-5 stages according to the Mogensen staging standard,and grouped according to the estimated glomerular filtration rate(e GFR)and urine protein level to estimate the progression risk of DKD,and classified into low risk group(L),medium risk group(M),High risk group(H)and extremely high risk group(EH).Secondly,general data(gender,age,BMI,blood pressure)and clinical data(such as the course of T2DM),fasting blood glucose(FBG),glycosylated hemoglobin(Hb A1c%),blood urea nitrogen(BUN),blood creatinine(Scr),e GFR,serum uric acid(SUA),cholesterol(TC),triglyceride(TG),high density lipoprotein(HDL-C),low density lipoprotein(LDL-C),albumin(ALB),24-hour urinary protein quantification(24h UTP),urinary protein excretion rate(UAER),urinary albumin to creatinine ratio(UACR),etc.),and 12 ml elbow venous blood was collected from the subjects.Serum exosomes were extracted by differential ultrafast centrifugation combined with filtration.Finally,real-time fluorescence quantitative PCR was used to detect the expression level of microRNA-1207-5p in exosomes,and medical statistics were used to analyze the statistical significance between micror NA-1207-5p and patients’ clinical indicators,so as to predict its clinical value in judging the risk of DKD progression.In addition,the general data and clinical indicators of patients with different stages and groups were analyzed to explore the suggestive role of each indicator on the degree of disease development in DKD patients.2.In the Web of science core collection,the previous research of microRNA-1207-5p is retrieved with specific keywords,and analyze the search results through the bibliometric software "Citespace",the current situation of its research in recent years can be mastered.Read the literature to summarize the LncRNA and mRNA that have been verified in previous research and can bind to microRNA-1207-5p adsorption,at the same time,use multiple websites to predict the new target genes of microRNA-1207-5p to build a ceRNA network.At the same time,in the DKD related datasets GSE51674 and GSE30528,the difference in the expression levels of microRNA-1207-5p and its predicted target genes was searched,and the box plot was drawn for visualization.Results:1.The UAER value is calculated by 24 h UTP,and according to the Mogensen staging standard,the patient is divided into five stages.The phases 1 and 2 with control group is combined into a normal proteinuria group,stage 3 is the microproteinary group,and stage 4 and 5 are combined to form a large number of proteinuria groups.Among them,there were 13 people in the normal proteinuria group,8 in the microproteinary group,and 41 in the proteinuria group.SPSS software analysis results show significant inter-group differences in course of disease,age,BMI,SBP,DBP,24 h UTP,UAER,UMALB,e GFR,UACR,SC,BUN,SUA,Ca,ALB,TG,HDL(p<0.05),and there was no significant difference between LDL,TC,P and FBG between the three groups(p>0.05).2.Calculate the e GFR of all subjects and combine with UMALB,the patients and the control group were divided into four groups according to the risk of progression of DKD,which include: low-risk group(L group,n=24);medium-risk group(M group,n=6);high-risk group(H group,n=12);and extremely high-risk group(EH group,n=20).The analysis results showed that among the four groups,there were no significant differences in course of disease,age,BMI,FBG,P,TC,TG,HDL and LDL(p>0.05),while there were significant differences in UAER,SBP,DBP,24 h UTP,UMALB,UACR,e GFR,SC,BUN,SUA,Ca and ALB(p<0.05).With the increase of the risk of progress,24 h UTP,UAER,UMALB,UACR and SC of each group showed an upward trend,and e GFR and ALB showed a downward trend.3.The Kruskal-Wallis H test is used to obtain the comparison of microRNA-1207-5p expression levels between four different progression risk groups,proving that there were significant statistical differences between groups(p=0.00<0.01).In different progressive risk groups,there are differences in microRNA-1207-5p expression,among which there are significant differences between low-risk groups,medium-risk groups and very high-progress risk groups(p<0.01),there are statistical differences between low-risk groups,medium-risk groups and high-progress risk groups(p<0.05),and there is no statistical difference between low-risk groups and medium-risk groups,high-risk groups and extremely high-risk groups(p>0.05).4.The correlation analysis of microRNA-1207-5p with the patient’s general data and clinical indicators is statistically analyzed using the Spearman correlation analysis method.The results show that the correlation analysis of microRNA-1207-5p with24 h UTP,UAER,UMALB,e GFR,UCR,SC,BUN,SUA,Ca and ALB has significant statistical significance(p<0.01),of which it is negatively correlated with 24 h UTP,UAER,UMALB,UACR,Scr,BUN,SUA(r=-0.470,-0.470,-0.508,-0.438,-0.532,-0.393,-0.425,p<0.01),and positive correlation with e GFR,Ca,ALB(r=0.460,0.457,0.467,p<0.05).5.The results of multi-ordered Logistic regression analysis show that microRNA-1207-5p(OR=0.996,95% CI:-0.008-0.000,p<0.05)is a protective factor for DKD progression.6.The ROC curve of microRNA-1207-5p and disease progression risk between each group is drawn.The results show that compared with L-M,L-H,L-EH,M-H,MEH and H-EH,the areas below the curve are: 0.397,0.859,0.877,0.847,0.850,0.529 respectively,which shows that microRNA-1207-5p is of significant significance as a prediction index of disease progression risk between low-risk groups and high-risk groups,very high-risk groups,medium-risk groups and high-risk groups.7.Bibliometric analysis results show that most of the studies of microRNA-1207-5p are completed by Chinese scholars.There are many studies in tumor diseases,and there is sufficient evidence that it is related to the occurrence of colorectal cancer,diabetic kidney disease and other diseases.Looking at previous studies,eight proven LncRNAs that can be combined with microRNA-1207-5p adsorption were screened(PVT1(some studies believe that PVT1 can be used as a host gene of microRNA-1207-5p),LUADT1,OR3A4,SNHG11,MIR194-2HG,LncRNA319,LncRNA BC032469,lnc-MMP22)and their downstream mRNA;four databases were used to predict the new target genes of microRNA-1207-5p,and a total of 13 genes were obtained.Compared with the results of renal tissue sequencing in the control group,the expression of microRNA-1207-5p in the kidneys of DKD patients was significantly reduced,while in the 13 target genes predicted,the expression level of PAX2 was increased.Conclusion: microRNA-1207-5p in the serum exosome of DKD patients shows a significant decrease in the increase of the disease risk.As a protective factor of DKD progression,it has important clinical value in the risk prediction of DKD progression.At the same time,the regulation of downstream target gene PAX2 by microRNA-1207-5p may act as a new mechanism to affect the occurrence and progression of DKD. |
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