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Sepsis is an important cause of acute kidney injury (AKI). About 60% of sepsis patients will develop AKI. At present, the standard of clinical diagnosis of AKI is still based on the changes in serum creatinine and urine volume. Because of its lag in time, it may lead to delay in treatment and increase the mortality. To find a new biomarker similar to "troponin" for the diagnosis of AKI, and to achieve the early diagnosis and prevention of AKI, is of great significance to reduce the mortality of AKI. In recent years, it has been found that tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can be used for early diagnosis of sepsis associated-acute kidney injury (SA-AKI). They also have important values in risk stratification, prognosis judgment, intervention and other aspects of SA-AKI. In this paper, the research progress of the application of TIMP-2 and IGFBP7 in SA-AKI is reviewed.
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Objective:To explore the predictive value of serum tissue inhibitor of metalloproteinases-2(TIMP-2), insulin-like growth factor-binding protein-7 (IGFBP-7), angiopoietin-2 (Ang-2) and laboratory examination indicators in patients with sepsis associated acute kidney injury (SAKI).Methods:Present study included 69 patients with sepsis, who were admitted to the emergency department of Peking University Third Hospital from April 2017 to August 2018. Within 72 hours of admission, 28 cases developed SAKI. General clinical features including sequential organ failure assessment (SOFA), acute physiological and chronic health status score Ⅱ (APACHE Ⅱ) and laboratory examination indicators including white blood cells (WBC), neutrophil/lymphocyte ratio (NLR), procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6), D-dimer, fibrinogen (Fib), urea, uric acid (UA) were analyzed and serum samples were obtained to detect the levels of biomarkers TIMP-2, IGFBP-7, and Ang-2. Multivariate logistic regression analysis was performed to determine independent risk factors of SAKI, and the receiver operating characteristic (ROC) area under the curve (AUC) was used to assess the early predictive value of biomarkers and laboratory examination indicators for SAKI.Results:Compared with the non-SAKI group, patients in the SAKI group had higher SOFA score, higher incidence of septic shock, higher NLR, PCT, CRP, D-dimer, and UA levels (all P<0.05). The levels of TIMP-2, IGFBP-7, TIMP-2×IGFBP-7 and Ang-2 in the SAKI group were 23.5 (17.3, 30.3)ng/ml, (185.6±47.2)ng/ml, 3.98(2.89, 6.00) (ng/ml) 2/1 000, 1 953 (950, 2 239) pg/ml respectively, which were significantly higher than those in the non-SAKI group (16.4[13.5, 22.4] ng/ml, [139.4±34.7]ng/ml, 2.28[1.57, 4.03](ng/ml) 2/1 000, 576[334, 1 076] pg/ml, respectively, all P<0.05). Logistic regression analysis showed that IGFBP-7 ( OR=1.039, 95%CI 1.000-1.079, P<0.05) and SOFA ( OR=1.521, 95%CI 1.144-2.022, P<0.05) are independent risk factors of SAKI. ROC curve analysis showed that the AUC of IGFBP-7 and SOFA scores for early prediction of SAKI was 0.805 (sensitivity 78.6%,specificity 78.3%), 0.832 (sensitivity 67.9%,specificity 82.9%) respectively. Combined both biomarkers, the AUC increased to 0.893 (sensitivity 82.1%, specificity 87.8%), the diagnostic performance was superior to IGFBP-7 or SOFA alone ( P<0.05). Conclusion:Elevated IGFBP-7 and SOFA are independent risk factors for sepsis associated acute kidney injury, and combined assessment with IGFBP-7 and SOFA can increase the diagnostic performance on the early detection of high-risk patients with SAKI.
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Objective:To investigate the serum level of insulin-like growth factor binding protein 7 (IGFBP7) in patients with gastric cancer and its diagnostic significance.Methods:A total of 100 gastric cancer patients (gastric cancer group) including 49 patients with early gastric cancer (early gastric cancer group) , who were hospitalized in Sun Yat-sen University Cancer Center from May to December 2019 were selected as the research subjects, and 94 physical examination subjects during the same period were selected as the normal control group. The levels of serum IGFBP7 were detected by enzyme-linked immunosorbent assay. At the same time, the laboratory carcinoembryonic antigen (CEA) test results were collected. The relationships between the level of serum IGFBP7 and the clinicopathological features of gastric cancer patients were analyzed. The diagnostic value was evaluated by receiver operating characteristic (ROC) curve.Results:The level of serum IGFBP7 in the gastric cancer group was (1.595±0.159) ng/ml, and that in the normal control group was (1.850±0.328) ng/ml, with a statistically significant difference ( t=-0.26, P<0.001) , and among them, the level of serum IGFBP7 in the early gastric cancer group was (1.601±0.153) ng/ml, and there was a statistically significant difference compared with the normal control group ( t=-0.26, P<0.001) . The level of serum CEA in the gastric cancer group was 2.230 (2.043) ng/ml, and that in the normal control group was 1.805 (1.020) ng/ml, with a statistically significant difference ( U=0.45, P=0.004) , and among them, the level of serum CEA in the early gastric cancer group was 2.220 (1.780) ng/ml, and there was a statistically significant difference compared with the normal control group ( U=0.53, P=0.002) . There were no significant correlations between IGFBP7 and CEA level ( χ2=0.36, P=0.547) , age ( χ2=0.16, P=0.688) , gender ( χ2=0.97, P=0.326) , depth of invasion ( χ2=0.30, P=0.585) , lymph node metastasis ( χ2=0.17, P=0.684) , distant metastasis ( χ2=0.09, P=0.767) and TNM stage ( χ2=0.38, P=0.537) . ROC curve analysis showed that the area under the curve (AUC) of IGFBP7 for gastric cancer diagnosis was 0.84 (95% CI: 0.78-0.89) , the AUC of CEA for gastric cancer diagnosis was 0.62 (95% CI: 0.54-0.70) , and there was a statistically significant difference ( Z=4.33, P<0.001) . The AUC of IGFBP7 combined with CEA for gastric cancer diagnosis was 0.85 (95% CI: 0.79-0.90) . Compared with CEA alone, there was a statistically significant difference ( Z=4.97, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.41, P=0.159) . The AUC of IGFBP7 in the diagnosis of early gastric cancer was 0.84 (95% CI: 0.78-0.91) , the AUC of CEA in the diagnosis of early gastric cancer was 0.66 (95% CI: 0.56-0.75) , and there was a statistically significant difference ( Z=3.11, P=0.002) . The AUC of IGFBP7 combined with CEA in the diagnosis of early gastric cancer was 0.85 (95% CI: 0.78-0.91) . Compared with CEA alone, there was a statistically significant difference ( Z=3.54, P<0.001) . Compared with IGFBP7 alone, there was no statistically significant difference ( Z=1.19, P=0.232) . Conclusion:The serum IGFBP7 level of gastric cancer patients is lower than that of normal controls. Compared with CEA, serum IGFBP7 has better diagnostic value for gastric cancer.
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Acute kidney injury (AKI) is a common complication in critically ill patients with complex etiology and high morbidity, which is closely related to the patient's mortality rate, hospital stay and long-term poor outcomes. Therefore, timely detection of AKI in the early reversible stage is particularly important to prevent its progression to renal failure and initiating renal replacement therapy. Therefore, exploring the relevant biomarkers in the occurrence and development of acute kidney injury has important clinical significance for the diagnosis and treatment of the disease. Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) are used as cell cycle arrest proteins, which has shown certain advantages in the early diagnosis, risk stratification, prognosis judgment, and treatment effect of acute kidney injury. Cell cycle arrest protein [TIMP-2]×[IGFBP-7] plays a role in acute kidney injury caused by various reasons and can be used as a reference index for disease prognosis.
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Objective:This study is to investigate the predictive value of serum levels of TIMP-2 and insulin-like growth factor-binding protein 7(IGFBP7) in patients with DCD(donation after cardiac death) kidney transplantation.Methods:A prospective research design was used to select DCD kidney transplant patients admitted to the Li Huili Hospital of Ningbo University from January 2018 to October 2020.Inclusion criteria: ①Complete data; ②There were no serious complications affecting the function of the transplanted kidney in the early postoperative period.Exclusion criteria: ①Incomplete data; ②Patients were unable or unwilling to cooperate with the study; ③Severe complications affecting the function of the transplanted kidney occurred early after the operation.The ELASE method was used to quantitatively detect the serum TIMP-2 and IGFBP7 levels at 6, 12, 24, 48, 72 hours and 7 days after renal transplantation, and monitor the serum creatinine values during the same period and 21 days after the operation. According to the occurrence of DGF, the measured values of TIMP-2 and IGFBP7 at different time points and their product's ability to predict the occurrence of DGF after kidney transplantation were analyzed. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the diagnostic efficacy of TIMP-2 and IGFBP7 for DGF.Results:A total of 33 patients were enrolled, 7 patients (21.2%) in the DGF group and 26 patients (78.8%) in the non-DGF group. Between the two groups, the donor glomerular filtration rate were [98.5(15.8-132.5)ml/(min·1.73m 2) and 79.1(60.6-102.5)ml/(min·1.73m 2)], recipient gender (male/female: 3/4 cases and 10/16 cases), recipient age [48(34-56) Years old and 45(23-61) years old], the recipient's preoperative creatinine [1114.0(731.4-1293.0)μmol/L and 858.4(657.6-1051.9)μmol/L], the recipient's preoperative urea nitrogen [15.0(13.2-19.6)mmol/L and 17.3(13.6-20.9)mmol/L], receptor preoperative albumin [43.5(38.5-45.3)mmol/L and 41.2(37.5-46.1) mmol/L], recipient dialysis method [hemodialysis/peritoneal dialysis: 3/4 cases and 9/17 cases], warm ischemia time [6(5-7) and 5(4-6) min, there was no statistically significant difference] ( P>0.05). The values of serum IGFBP7 and TIMP-2×IGFBP7 in the DGF group were higher than those in the non-DGF group at all time points ( F=15.753, P=0.040; F=13.000, P=0.024), while serum TIMP-2 was not significant between the two groups difference ( F=1.157, P=0.075). For the diagnostic value of DGF, the AUC of serum IGFBP7 at 48 h after surgery was 0.863 (95% CI 0.696-1.000, P=0.004). When 5.97 ng/ml was used as the cut-off value, the sensitivity was 85.7% and the specificity was 80.8 %. The AUC of TIMP-2×IGFBP7 at 48 hours after surgery was 0.819 (95% CI 0.641-0.996, P=0.011). When 62.06(ng/ml) 2 was used as the cutoff value, the sensitivity was 71.4% and the specificity was 80.8%.There was no statistical difference in the area under the curve between the two ( P>0.05). There were differences in the dynamic trend of serum IGFBP7 and creatinine in the DGF group. Serum IGFBP7 at 7 days after surgery was positively correlated with creatinine at 21 days after surgery. Conclusion:Serum IGFBP7 and TIMP-2×IGFBP7 could predict the occurrence of DGF after DCD donor kidney surgery. The predictive value changes with time. Among them, 48h and 7d after surgery are the most valuable. However, serum TIMP-2 has not been found to have predictive value in this study.
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Objective To explore the feasibility and accuracy of urinary tissue inhibitor of metalloproteinase-2(TIMP-2) and insulin-like growth factor binding protein-7(IGFBP-7) for predicting acute kidney injury(AKI) occurrence in pediatric patients with sepsis.Methods A total of 174 pediatric patients with sepsis in PICU of Chengdu Municipal Women and Children Central Hospital and 30 healthy control children(control group) from March 2014 to March 2017 were included.Fasting venous blood was collected at 8:00 every morning during 7 d before admitting to PICU for detecting serum SCr level;fresh urine sample was taken at 8:00 am and 20:00 pm.for detecting TIMP-2 and IGFBP-7 levels.The AKI was diagnosed according to KDIGO criteria in 2012.Thus the septic children patients were divided into the AKI group and non-AKI group.The receiver operating characteristic(ROC) curve and the area under the curve(AUC) were adopted to analyze the predictive value of TIMP-2 and IGFBP-7 at 12,24,36,48 h before diagnosis for AKI.Results Within 7 d in 174 children cases admitting to PICU,52 cases(29.89％) were diagnosed as AKI.The TIMP-2 and IGFBP-7 levels had no statistical difference between the non-AKI group and control group(P＞0.05).Urinary TIMP-2 and IGFBP-7 levels at 12,24,36 h before diagnosing AKI were significantly increased compared with those at admitting to PICU(P＜0.01);AUC of urinary TIMP-2 and IGFBP-7 levels for predicting AKI occurrence within following 12,24,36 h were 0.967 (95 ％CI:0.946-0.989),0.898(95％CI:0.844-0.951) and 0.748(95％CI:0.669-0.827) respectively,the difference was statistically significant(P＜0.01).Conclusion The urinary TIMP-2 and IGFBP-7 increase can more accurately predict AKI occurrence in pediatric patients with sepsis.
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Objective:To investigate the effects of insulin-like growth factor binding protein 7 gene on the biological characteristics of colorectal cancer.methods:human colorectal cancer SW480 cells were cultured.According to the different transfectants,the cells were divided into IGFBP7 plasmid group,blank plasmid group and control group.The expression of IGFBP7 gene was detected by RT-PCR.MTT assay was used to detect cell proliferation.Flow cytometry was used to detect the apoptotic rate.Transwell chamber was used to detect cell migration and cell invasion.Results:The relative expression levels of IGFBP7 mRNA in IGFBP7 plasmid group was higher than which in the blank plasmid group and the control group,the difference was statistically significant (P＜0.05).Compared with the blank plasmid group and the control group,the A values at 24h,48h,72h and 96h in the IGFBP7 plasmid group were decreased,the differences were statistically significant(P＜0.05).Compared with the blank plasmid group and the control group,the apoptosis rate in the IGFBP7 plasmid group was increased,the difference was statistically significant (P＜0.05).The number of migrating cells and the number of invasive cells in IGFBP7 plasmid group were lower than those in the blank plasmid group and the control group,the differences were statistically significant (P＜0.05).Conclusion:Overexpression of IGFBP7 gene could inhibit proliferation of colorectal cancer cells,accelerate cell apoptosis,reduce cell migration and cell invasion.
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Objective To evaluate the early diagnostic value of urinary insulin-like growth factor binding protein-7 (IGFBP-7) in sepsis-induced acute kidney injury (AKI),and to compare the effects of urinary IGFBP-7 to that of serum cystatin-C (sCys-C) and serum creatinine (sCr) on predicting the severity of sepsis-induced AKI patients.Methods A total of 105 patients with sepsis admitted to ICU in Tianjin First Hospital from September 2015 to August 2016 were divided into AKI group (n =48) and non-AKI group (n =57) according to the AKI diagnostic criteria.The samples of blood and urine of the patients were collected at 0,3,6,12,24 and 48 h,to measure the levels of urinary IGFBP-7,and serum Cys-C and sCr.Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC),the early diagnostic value of urinary IGFBP-7,and serum sCys-C and sCr in sepsis-induced AKI patients was determined.Results With the increase in length of ICU stay,the levels of urinary IGFBP-7,and serum sCys-C and sCr in AKI patients increased gradually.There was a significant difference between the two groups in the level of IGFBP-7 at 3 h [2.34 (2.03,4.19) ng/mL vs.1.79 (1.51,2.62) ng/mL,P ＜0.05].At 6 h,the difference in sCys-C between two groups was statistically significant [(1.63 ± 0.42)ng/mL vs.(1.20 ±0.46) ng/mL,P ＜ 0.05].At 12 h,the difference in sCr between two groups was statistically significant [80.5 (74.3,88.0) ng/mL vs.77.0 (67.0,84.0) ng/mL,P ＜ 0.05].The AUCs of urinary IGFBP-7 and sCys-C of sepsis-induced AKI patients were 0.881 (95％ CI:0.813-0.949) and 0.782 (95％ CI:0.692-0.872),which were superior to those in AUC of sCr 0.629 (95％CI:0.522-0.737).When the cutoff value of urinary IGFBP-7 was 1.82 ng/mL,the sensitivity was 93.8％ and the specificity was 77.2％.Conclusions Urine IGFBP-7 and sCys-C have higher predictive value in sepsis-induced AKI than sCr,whereas urine IGFBP-7 is more sensitive and specific than sCys-C,suggesting that IGFBP-7 may be used as sepsis signs of early diagnosis of AKI.
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Objective To evaluate the early diagnostic value of urinary insulin-like growth factor binding protein-7 (IGFBP-7) in sepsis-induced acute kidney injury (AKI),and to compare the effects of urinary IGFBP-7 to that of serum cystatin-C (sCys-C) and serum creatinine (sCr) on predicting the severity of sepsis-induced AKI patients.Methods A total of 105 patients with sepsis admitted to ICU in Tianjin First Hospital from September 2015 to August 2016 were divided into AKI group (n =48) and non-AKI group (n =57) according to the AKI diagnostic criteria.The samples of blood and urine of the patients were collected at 0,3,6,12,24 and 48 h,to measure the levels of urinary IGFBP-7,and serum Cys-C and sCr.Based on the receiver operating characteristic curve (ROC) and the area under the curve (AUC),the early diagnostic value of urinary IGFBP-7,and serum sCys-C and sCr in sepsis-induced AKI patients was determined.Results With the increase in length of ICU stay,the levels of urinary IGFBP-7,and serum sCys-C and sCr in AKI patients increased gradually.There was a significant difference between the two groups in the level of IGFBP-7 at 3 h [2.34 (2.03,4.19) ng/mL vs.1.79 (1.51,2.62) ng/mL,P ＜0.05].At 6 h,the difference in sCys-C between two groups was statistically significant [(1.63 ± 0.42)ng/mL vs.(1.20 ±0.46) ng/mL,P ＜ 0.05].At 12 h,the difference in sCr between two groups was statistically significant [80.5 (74.3,88.0) ng/mL vs.77.0 (67.0,84.0) ng/mL,P ＜ 0.05].The AUCs of urinary IGFBP-7 and sCys-C of sepsis-induced AKI patients were 0.881 (95％ CI:0.813-0.949) and 0.782 (95％ CI:0.692-0.872),which were superior to those in AUC of sCr 0.629 (95％CI:0.522-0.737).When the cutoff value of urinary IGFBP-7 was 1.82 ng/mL,the sensitivity was 93.8％ and the specificity was 77.2％.Conclusions Urine IGFBP-7 and sCys-C have higher predictive value in sepsis-induced AKI than sCr,whereas urine IGFBP-7 is more sensitive and specific than sCys-C,suggesting that IGFBP-7 may be used as sepsis signs of early diagnosis of AKI.
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Objective To present study was to investigate the effects of insulin-like growth factor binding protein 7 (IGFBP7)on the proliferation of human hepatocellular carcinoma HepG2 cells.Methods Human hepatocellular carcinoma HepG2 cells was cultured,and plasmid pIRES2-ZsGreen1-IGFBP7 or empty plasmid was transfected into HepG2 cells and the cell transfection efficiency was examined by fluores-cence microscopy;MTT was performed to evaluate the effect of IGFBP7 on proliferation and apoptosis of HepG2 cells in 48 hours after transfection.Results IGFBP7 transfected group decreased cell proliferation noticeably.Conclusions Overexpression of IGFBP7 can down-regulte the proliferation of human hepatocel-lular carcinoma HepG2 cells.
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Objective To assess the relationship of methylation status of CpG islands in the promoter region of insulin-like growth factor binding protein 7 (IGFBP7) gene with the expression of IGFBP7 gene in human melanoma cell lines and primary melanocytes.Methods Primary melanocytes from human forcskin tissue as well as 4 human melanoma cell lines,including A375,M14,SK-MEL-1 and MV3,were used in this study.Bisulfite sequencing PCR (BSP) was applied to detect the methylation status of 54 CpG sites in the 5'-flanking promoter region of IGFBP7 gene in all of the melanoma cell lines and primary melanocytes.Results As hierarchical cluster analysis showed,IGFBP7-positive cells (including A375,M14 and SK-MEL-1 ) differed significantly from IGFBP7-negative cells (including MV3 cells and primary melanocytes) in the methylation pattern of IGFBP7 gene promoter region.Conclusion The methylation status of CpG island in the promoter region of IGFBP7 gene may be associated with its expression in melanoma cell lines.
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Insulin-like growth factor binding protein 7 exert modulatory function in insulin-like growth factor/insulin(IGF/INS) protein network by carrying and transiting IGF/INS,or prolonging their half-life.IGFBP7 has strong ability to bind insulin and low affinity to IGFs and plays a role in either IGFs-dependent way or IGFs-independent way.IGFBP7 involves in multiple function such as cell proliferation,adhesion,invasion,migration and tumor vascular formation through several signaling pathways.
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Objective To study the effects of 5-aza-dc on the expression of IGFBP7 in and proliferation of melanoma cell lines A375 and M14.Methods Reverse transcription-PCR and immunocytochemistry were performed to detect the mRNA and protein expression of IGFBP7 in A375 cells and M14 cells after treatment with 5-aza-dc of 10μmol/L for 48 hours,and MTT assay to measure the proliferation of both cell lines treated with 4 different concentrations (2.5,5,10,20μmol/L) of 5-aza-dc for various durations.Results The treatment with 5-aza-dc restored IGFBP7 expression at both mRNA and protein levels.The four concentrations of 5-aza-dc inhibited the proliferation of A375 and M14 cells in a dose-dependent (F=561.12,271.43,respectively,both P<0.01) and time-dependent (F=141.35,549.33,respectively,both P<0.01) manner.Conclusions DNA methylation may be involved in the modulation of aberrant IGFBP7 gene expression in melanoma,and 5-aza-dc could inhibit the proliferation of A375 and M14 cells.
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Objective To investigate the regulatory effect of insulin-like growth factor binding protein 7 (IGFBP7) on the synthesis and secretion of fibronection and the inhibiting effect of anti-IGFBP7 antibody on apop-tosis of hepatic stellate cell-T6 (HSC-T6). Methods HSC-T6 cultured in vitro were divided into blank control group, IGFBP7 20 μg/L group, anti-IGFBP7 antibody 0.25 mg/L group, anti-IGFBP7 antibody 0.50 mg/L group and anti-IGFBP7 antibody 1.00 mg/L group. HSC-T6 were treated by IGFBP7 for 24 hours, then the expression of fibronectin was detected by Western blot and the content of fibronectin by ELISA. After incubating HSC-T6 with anti-IGFBP7 antibody for 14 hours, the inhibiting effect of anti-IGFBP7 antibody on HST-T6 was evaluated by MTT assay, and the effect of anti-IGFBP7 on the apoptosis of HST-T6 was detected by flow cytometry. All data were analyzed by one-way ANOVA, t test and SNK-q test. Results The content and expression of fibronection in IGFBP7 20 mg/L group were significantly higher than those in the blank control group (t = 22.06, 7.43, P < 0.05). Anti-IGFBP7 antibody had an obvious inhibiting effect on the proliferation of HSC-T6 (F=14. 70, P < 0.05), and it also enhanced the ratio of apoptosis of HSC-T6 (F = 63.79, P < 0.05). Conclusions IGFBP7 can increase the synthesis and secretion of fibronectin which is the principal component of extracellular matrix. Anti-IGFBP7 antibody can inhibit the proliferation and promote the apoptosis of HSC-T6.
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In the present study, we performed immunohistochemical studies to investigate the detailed distribution of insulin-like growth factor binding protein 7 (IGFBP7) in the central nervous system of adult rats. Twelve adult (4~6 month old) Sprague-Dawley rats were examined in this study. Immunohistochemistry using specific antibodies against IGFBP7 was performed in accordance with the free-floating method. In the present study, IGFBP7 immunoreactivity was observed in the cerebral cortex, hippocampus, brainstem, cerebellum and spinal cord. In the cerebral cortex, heavily stained neurons were seen in layers II-VI. In the hippocampus, pyramidal cells in CA1-3 region were strongly immunoreactive for IGFBP7. Strong immunoreactive neurons were also found in the supraoptic nucleus, paraventricular nucleus, periaqueductal gray and oculomotor nucleus. In the cerebellum, IGFBP7 immunoreactivity was prominent in the Purkinje cells and cerebellar output neurons. IGFBP7-immunoreactive neurons were prominent in the superior vestibular nucleus, cochlear nucleus, trigeminal motor nucleus, nucleus of the trapezoid, and facial nucleus. IGFBP7-immunoreactive neurons were also observed mainly in the anterior horn of the spinal cord. The first demonstration of IGFBP7 localization in the whole brain may provide useful data for the future investigations on the structural and functional properties of IGFBP7.