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Objective:To explore the expression levels and the clinical significance of serum secreted frizzled-related protein 5 (SFRP5) and miR-124-3p in patients with hypertension during pregnancy.Methods:Ninety-eight patients with hypertension during pregnancy diagnosed from Jan. 2019 to Feb. 2022 were selected as the observation group. According to the degree of the condition of patients, they were divided into 41 cases of pregnancy hypertension, 32 cases of mild preeclampsia, and 25 cases of severe preeclampsia, and 80 healthy subjects during the same period were selected as the control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression level of serum SFRP5 in patients, real-time fluorescence quantitative method (qRT-PCR) was used to detect the expression level of miR-124-3p. The relationship between SFRP5, miR-124-3p levels and clinicopathological indicators in patients with hypertension in pregnancy was analyzed, Pearson correlation analysis was used to analyze the correlation between SFRP5 and miR-124-3p. Multivariate Logistic regression was used to analyze the risk factors of hypertension in pregnancy.Results:Compared with the control group, the serum SFRP5 expression level of the observation group [ (33.78±5.21) ng/L vs (43.34±8.56) ng/L] was down-regulated, while the miR-124-3p level [ (2.16±0.41) vs (1.01±0.17) ] was up-regulated, and the serum SFRP5 level of the observation group decreased with the severity of the disease[ (38.43±6.37) ng/L (33.18±5.14) ng/L (26.94±3.38) ng/L], while the level of miR-124-3p increased with the severity of the disease[ (1.62±0.24) (2.19±0.43) (3.01±0.69) ], the difference was statistically significant ( P<0.05) . The expression levels of SFRP5 and miR-124-3p in the serum of patients with hypertension in pregnancy were related to the age, pregnancy, pre-pregnancy BMI, and fasting blood glucose level of patients ( P<0.05) , but not related to the gestational age of patients ( P>0.05) . Bioinformatics TargetScan website showed that SFRP5 and miR-124-3p had binding sites. Pearson correlation analysis showed that SFRP5 and miR-124-3p were negatively correlated ( r=-0.610, P<0.05) . Multivariate Logistic regression analysis showed that SFRP5 was a protective factor for pregnancy-induced hypertension in pregnant women, and miR-124-3p was a risk factor ( P<0.05) . Conclusion:The serum levels of SFRP5 and miR-124-3p are abnormally expressed in patients with hypertension during pregnancy, and there is a certain relationship with the degree of disease. Both are involved in the occurrence and development of hypertension during pregnancy.
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Objective:To investigate the expression and correlation of serum trefoil factor 3 (TFF3), serum secreted frizzled-related protein 5 (SFRP5), galectin-3 (Gal-3), and nesfatin-1 (NES-1) in patients with type 2 diabetes(T2DM), diabetic nephropathy(DN), chronic kidney disease (CKD), and healthy controls. To explore the relationship between the above factors and the diagnosis of DN and to establish a diagnostic formula for the diagnosis of DN combined with the above four factors.Methods:In each group 36 patients hospitalized in Tianjin Third Central Hospital from April 2017 to June 2019 were enrolled. 36 healthy volunteers were also chosen as the healthy control group. After 8 to 10 hours of fasting, the venous blood of the subjects in each group was centrifuged, the serum was collected for detection, the serum levels of TFF3, SFRP5, Gal-3, and NES-1 were compared, and the Pearson correlation analysis was performed. According to whether the diagnosis of DN was repeated, the subjects were divided into the DN group and the non-DN group (including a healthy control group, T2DM group, and CKD group). The four datasets were analyzed by binary logistic regression, and the diagnostic prediction model of DN was established, which was further verified by receiver operating characteristic (ROC).Results:The serum levels of TFF3, Gal-3 and NES-1 in DN groups were significantly higher than those in healthy control group, T2DM group and CKD group (all P<0.05), but the serum level of SFRP5 in DN group was significantly lower than that in healthy control group, T2DM group and CKD group (all P<0.05). The differences between the four groups in the four aforementioned indicators were all statistically significant (all P<0.001). The Pearson correlation analysis showed that there was a significant correlation between the above four indicators (all P<0.01). The area under the ROC curve of TFF3, SFRP5, Gal-3, and NES-1 was 0.849, 0.807, 0.882, and 0.841 respectively. The area under the curve diagnosed by the combination of four indicators (0.986) was significantly higher than that of a single indicator, and the difference was statistically significant ( Z=3.75, 4.08, 3.63, 4.06, all P<0.05). Conclusions:The joint prediction model based on serum TFF3, SFRP5, Gal-3, and NES-1 can effectively improve the diagnostic accuracy of DN and provide an important basis for clinical diagnosis of DN.
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Abstract Introduction: Obstructive sleep apnea, a common disease, is usually complicated by insulin resistance and type 2 diabetes mellitus. Adipokine is considered to play an important role in the development of insulin resistance and type 2 diabetes mellitus in obstructive sleep apnea. Objective: To assess whether secreted frizzled-related protein 5, a new adipokine, is involved in untreated obstructive sleep apnea patients. Methods: Seventy-six subjects with obstructive sleep apnea and thirty-three control subjects without obstructive sleep apnea were recruited and matched in terms of body mass index and age. The fasting secreted frizzled-related protein 5 plasma concentration was tested using ELISA. In addition, the correlation between secreted frizzled-related protein 5 and the homeostasis model assessment of insulin resistance was obtained. Multiple linear regression analysis models with stepwise selection were performed to determine the independent associations between various factors and secreted frizzled-related protein 5. Results: Plasma secreted frizzled-related protein 5 levels were significantly lower in the obstructive sleep apnea group than in the control group (obstructive sleep apnea group: 28.44 ± 13.25 ng/L; control group: 34.16 ± 13.51 ng/L; p = 0.023). In addition, secreted frizzled-related protein 5 was negatively correlated with homeostasis model assessment of insulin resistance but positively correlated with the mean and lowest oxygen saturation with or without adjusting for age, gender, body mass index, neck circumference, waist circumference and waist-to-hip ratio. The multiple linear regression analysis showed there was an independent negative association between secreted frizzled-related protein 5 and homeostasis model assessment of insulin resistance. Conclusion: Secreted frizzled-related protein 5 was involved in obstructive sleep apnea and the decrease in secreted frizzled-related protein 5 was directly proportional to the severity of obstructive sleep apnea. There was an independent negative correlation between homeostasis model assessment of insulin resistance and secreted frizzled-related protein 5 in the obstructive sleep apnea group. Secreted frizzled-related protein 5 might be a therapeutic target for insulin resistance in obstructive sleep apnea.
Resumo Introdução: A apneia obstrutiva do sono, uma doença comum, é geralmente complicada com resistência à insulina e diabetes melito tipo 2. Acredita-se que a adipocina possa ter um papel importante no desenvolvimento de resistência à insulina e diabetes melito tipo 2 na apneia obstrutiva do sono. Objetivo: Avaliar se a proteína secretada relacionada ao receptor frizzled-5, uma nova adipocina, está envolvida em pacientes com apneia obstrutiva do sono não tratada. Método: Foram recrutados 76 indivíduos com apneia obstrutiva do sono e 33 indivíduos controle sem apneia obstrutiva do sono e pareados em relação a índice de massa corporal e idade. A concentração plasmática de proteína secretada relacionada ao receptor frizzled-5 foi testada em jejum com o teste Elisa. Além disso, obteve-se correlação entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Modelos de análise de regressão linear múltipla com seleção stepwise foram feitos para determinar as associações independentes entre vários fatores e a proteína secretada relacionada ao receptor frizzled-5. Resultados: Os níveis plasmáticos de proteína secretada relacionada ao receptor frizzled-5 foram significativamente menores no grupo com apneia obstrutiva do sono do que no grupo controle (grupo com apneia obstrutiva do sono: 28,44 ± 13,25 ng/L; grupo controle: 34,16 ± 13,51 ng/L; p = 0,023). Além disso, a proteína secretada relacionada ao receptor frizzled-5 foi correlacionada negativamente com o modelo de avaliação da homeostase de resistência à insulina, mas se correlacionou positivamente com a média e a saturação mínima de oxigênio com ou sem ajuste para idade, gênero, índice de massa corporal, circunferência do pescoço, circunferência da cintura e relação cintura-quadril. A análise de regressão linear múltipla mostrou que houve uma associação negativa independente entre a proteína secretada relacionada ao receptor frizzled-5 e o modelo de avaliação da homeostase de resistência à insulina. Conclusões: A proteína secretada relacionada ao receptor frizzled-5 esteve envolvida na apneia obstrutiva do sono e sua diminuição foi diretamente proporcional à gravidade da apneia obstrutiva do sono. Houve uma correlação negativa independente entre o modelo de avaliação da homeostase de resistência à insulina e a proteína secretada relacionada ao receptor frizzled-5 no grupo da apneia obstrutiva do sono. A proteína secretada relacionada ao receptor frizzled-5 pode ser um alvo terapêutico para a resistência à insulina na apneia obstrutiva do sono.
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Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Insulin Resistance/physiology , Sleep Apnea, Obstructive/blood , Diabetes Mellitus, Type 2/complications , Eye Proteins/blood , Membrane Proteins/blood , Body Mass Index , Case-Control Studies , Adaptor Proteins, Signal Transducing , Insulin/blood , Obesity/complicationsABSTRACT
Obj ective To investigate the mechanism of secreted frizzled-related Protein 5 ( sFRP5) expression in cardiomyocyte hypertrophy.Methods In vivo experiment, neonatal rat ventricular myocytes were exposed to Ang Ⅱ(10-6 mmol/L, 48 h).Telmisartan, Y27632, PD98059,SB203580 and SP600125 were used to block angiotensin type 1 receptor( AT1R) , Rho/ROCK, p38 MAPK, ERK1/2 and JNK pathway, respective-ly.Western blot was applied to determine the expressions of sFRP5, ROCK1, ROCK2, total MYPT1, p-MYPT1.RT-PCR was used to determine sFRP5 expression.Results There was significant inhibition of sFRP5 expression when treated with Y37632 and SP699125, but less with SB203580 and PD98059 in AngⅡ-induced cardiomyocytes.Moreover, telmisartan down-regulated the expression of ROCK1, but no effect on the expression of ROCK2.Conclusions The expression of sFRP5 is up-regulated mainly by Rho/ROCK1/JNK pathway in cardiomyocyte hypertrophy induced by Ang Ⅱ.
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Objective To investigate the levels of serum Wnt5a and Sfrp5 in elderly male patients with type 2 diabetes mellitus (T2DM), and identify associations between their levels and glycemic control. Methods A total of 67 elderly male T2DM patients and 65 nondiabetic subjects were studied. Participants were divided into four groups:normal control (NC group), T2DM patients were categorized by HbA1C quartile(Group Ⅰ: HbA1C<7％, Group Ⅱ:7％≤HbA1C < 9％, Group Ⅲ: HbA1C ≥9％). The serum Wnt5a and Sfrp5 concentrations were measured through ELISA. Influencing factors for Wnt5a and Sfrp5 were analyzed. Results Compared with the NC group, Wnt5a levels of elderly T2DM were decreased in groups Ⅱ and Ⅲ, in contrast, Sfrp5 levels were elevated in groups Ⅱ and Ⅲ than NC group(all P<0.05). Spearman correlation analysis suggested that Wnt5a levels were negatively correlated with HbA1C , GA, FPG, and 2hPG(r were -0.277, -0.298, -0.185, and -0.254 respectively, all P<0.05);Sfrp5 levels were positively correlated with HbA1C , GA, and FPG(r were 0.311, 0.247, and 0.200 respectively, all P<0.05) while negatively correlated with BMI and LDL-C( r were - 0.193 and - 0.190, both P< 0.05). Multivariate linear regression analysis showed that HbA1C was an independent association factor for Wnt5a, and FPG was an independent association factor for Sfrp5. Conclusions In the elderly male T2DM with worse glycemic control, Wnt5a levels were more decreased, and in contrast, Sfrp5 levels were elevated. This result indicated that Wnt5a and Sfrp5 may be associated with the level of glycemic control in elderly male T2DM patients.
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Objective To investigate the relationships between plasma secreted frizzled-related protein (SFRP) 5 level with type 2 diabetes (T2DM ) and carotid atherosclerosis (CAS). Methods According to the results of carotid color Doppler ultrasound ,56 T2DM patients were divided into 28 with carotid atherosclerosis (CAS group) and 28 without carotid atherosclerosis (NAS group). 28 healthy volunteers served as normal control (NC group). Serum SFRP5 was measured by ELISA. Results The level of serum SFRP5 in T2DM patients was lower than NC group (114.36 ± 25.48) vs (48.19 ± 11.82) , (43.88 ± 8.19)pg/ml ,(P 0.05 ]. Pearson correlation analysis showed that serum SFRP5 was negatively correlated with age ,TG ,hsC-RP ,FPG ,FIns , HOMA-IR ,HbA1c ,TC ,LDL-C and BMI (P0.05). Multiple linear regression results showed that age ,FIns and HbA1 c were independent influencing factors of serum SFRP5. Conclusion SFRP5 may be a protective factor for T2DM by ameliorating insulin resistance which may provide a new clue for the prevention and treatment of T 2DM.
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Objective T o investigate the relationship betw een the expression of secreted frizzled-related protein 5 (SFR P5) m RNA and the tim e interval after skeletal m uscle injury in rats by real-tim e PC R . Methods A total of ninety SD rats w ere random ly divided into the contusion groups at different tim es including 4 h, 8 h, 12 h, 16 h, 20 h, 24 h, 28 h, 32 h, 36 h, 40 h, 44 h, 48 h after contusion, incision groups at different tim es including 4h and 8h after incision and the control group. T he sam ples w ere taken from the contused zone at different tim e points. T he total RNA w as isolated from the sam ples and re-versely transcribed to analyze the expression levels of SFRP5 m RNA . Results C om pared to the control group, the expression of SFRP5 m RNA in contusion groups w ere dow n-regulated w ithin 48 h after con-tusion and reached the low est level at 20 h, and the expression of SFRP5 m RNA gradually increased from 20 h to 48 h after contusion. T he expression of SFRP5 m RNA in the incised groups w ere signifi-cantly low er than that of the contusion groups at 4 h after injury. A t the tim e of 8 h, the expression levels betw een the contusion and incision groups show ed no statistically significant difference. Conclusion It is suggested that SFRP5 m RNA analysis m ay show regular expression and can be a m arker for estim ation of skeletal m uscle injury age.
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Objective To investigate the change expression levels of secreted frizzled related protein 5 (SFRP5) mRNA and protein in human adipose,and muscle tissues and the relationship between SFRP5 and insulin resistance in different glucose tolerance subjects.Methods Twelve type 2 diabetes mellitus(T2DM) patients and 12 aged and sex-matched healthy control subjects were enrolled.T2DM patients were diagnosed by1999 WHO criterion.Under the same conditions,the omental adipose and muscle tissues from these patients undergoing elective abdominal surgery were obtained.Expressions of sfrp5 protein and mRNA in adipose and muscle tissues were determined by semi—quantitive RT-PCR and Western blot while body height,weight,waist circumference,hipcircumference,blood pressure,lipodemia,fasting plasma glucose,fasting insulin,glycosylated hemoglobin,fasting serum insulin(FINS),HOMA-β,HOMA-insulin resistance index(HOMA-IR) etc were investigated.Results 1.SBP,TG,FPG,2 h PG,Fins,HOMA-IR,HbA1C were significantly higher in T2DM groups than in the control group.2.The expressions of SFRP5 mRNA and protein in omental adipose tissues were significantly higher inT2DM group than in the control group(P ＜ 0.01).3.The level of SFRP5 mRNA and protein expressions were higher in omental adipose tissue than in the muscle tissues.Conclusions The fact that mRNA and protein expression level of SFRP5 was higher in adipose tissue than in muscle indicates adipose tissue may be the main source of SFRP5.The expressions of SFRP5 mRNA and protein were higher inT2DM group than in the control group indicates sfrp5 may play a role in insulin resistance.
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Diabetic rat model accompanied by insulin resistance was established by intraperitoneal injection of streptozocin.Following metformin treatment for 5 weeks,ELISA was used to detect the level of plasma secreted frizzled-related protein (SFRP) 5,and immunohistochemistry was used to detect the expression of p-JNK in the liver.insulin resistance(IR) and p-JNK were significantly increased in diabetic group compared with the control group (P＜0.05),while plasma SFRP5 level was reduced (P＜0.01).After metformin treatment,the plasma SFRP5 levels were significantly increased (P＜0.05),while IR and p-JNK was decreased (P＜O.05).Metformin may ameliorate insulin resistance via upregulating the SFRP5 expression of diabetic rats.
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To investigate the relationships among plasma secreted frizzled-related protein ( sfrp) 5 level and body fat parameters, glucolipid metabolism, insulin resistance index, and inflammation. 89 subjects with normal glucose tolerance(NGT) and 87 patients with type 2 diabetes mellitus (T2DM) were enrolled and each group was divided into no-obese and obese subgroups. Obesity was defined as body mass index ( BMI)≥25 kg/m2 according to the World Health Organization -Western Pacific Region diagnostic criteria ( 2000 ) . Body fat parameters were measured and BMI, waist-hip ratio were evaluated, meanwhile, the levels of blood glucose-lipid parameters and fasting insulin were also determined. Insulin resistance index ( IR) was assessed by homeostasis model assessment ( HOMA) . The concentrations of plasma sfrp5 and interleukin 6 were detected by enzyme-linked immunosorbent assay. Plasma sfrp5 level in T2DM group was significantly lower than that in NGT group [(8. 35±3. 38 vs 11. 35±3. 69)ng/ml, P<0. 01]. The levels of plasma sfrp5 in subjects with obesity were also lower than those in subjects with no-obesity in both NGT and T2DM groups [(9. 46±2. 70 vs 13. 12±3. 62)ng/ml and(6. 70±2. 34 vs 10. 12±3. 45) ng/ml, both P<0. 01]. Plasma concentrations of sfrp5 in T2DM-obese group were significantly lower than that in NGT-obese group(P<0. 01). Correlation analysis showed that plasma sfrp5 levels were negatively correlated with waist-hip ratio, HbA1C, fasting insulin, triglycerides, waist circumference, fasting plasma glucose, interleukin 6, natural logarithm of HOMA-IR [ln(HOMA-IR)], and BMI(P<0. 01 or P<0. 05). Multiple linear regression showed that ln(HOMA-IR), BMI, triglycerides were independent related factors in influencing the levels of plasma sfrp5 (r2=0. 216, 0. 177, 0. 113, all P<0. 05). Plasma sfrp5 levels were decreased in obesity and T2DM subjects and were correlated with body fat disposition, glucose-lipid metabolism, insulin resistance and inflammation. Lack of sfrp5 may contribute to the pathophysiology of obesity and T2DM.