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Objective:To observe the expression of angiopoietin-like protein 4 (ANGPTL4) signaling pathway in adenine-induced chronic kidney disease (CKD) rat model, and to explore the role of this pathway in renal fibrosis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into control group (saline, intragastric administration, n=15) and CKD group (250 mg·kg -1·d -1 2.5% adenine, intragastric administration, n=21). At the end of the 1st, 2nd and 4th week, 5 rats were randomly selected from each group. Renal function and 24-hour urinary protein quantity were measured. HE and Masson staining were used to observe the pathological changes of kidneys. Immunohistochemistry and real-time PCR were used to detect renal protein and mRNA expressions of hypoxia-inducible factor-1α (HIF-1α), ANGPTL4, bone morphogenetic protein 7 (BMP7), Smad1, α-smooth muscle actin (α-SMA) and type Ⅰ collagen (Col-Ⅰ). Pearson correlation analysis was used to analyze the correlation between the different indicators. Results:(1) Compared with the control group, the expression levels of serum creatinine and blood urea nitrogen in CKD group were higher at each time point, and the expression levels of 24-hour urinary protein quantity were higher at the end of the 2nd and 4th week (all P < 0.05). (2) HE and Masson staining showed that there were obvious renal structural disorders and collagen fiber deposition at each time point in CKD group compared with the control group, which got worse with time. (3) The results of immunohistochemistry and real-time PCR showed that compared with the control group, the protein and mRNA expression levels of ANGPTL4, α-SMA and Col-Ⅰ were higher, while the protein and mRNA expression levels of BMP7 and Smad1 were lower at the end of the 1st, 2nd and 4th week, and the protein and mRNA expression levels of HIF-1α were higher at the end of 2nd and 4th week in CKD group (all P < 0.05). (4) Correlation analysis results showed that HIF-1α and ANGPTL4 mRNA expression were positively correlated with α-SMA mRNA ( r=0.919, P < 0.001; r=0.757, P < 0.001), and also positively correlated with Col-Ⅰ mRNA ( r=0.925, P < 0.001; r=0.777, P < 0.001). HIF-1α mRNA expression was positively correlated with ANGPTL4 mRNA ( r=0.766, P < 0.001). There were significant negative correlations between HIF-1α, ANGPTL4 mRNA and BMP7 mRNA ( r=-0.652, P < 0.001; r=-0.741, P < 0.001). Conclusions:ANGPTL4 signaling pathway may be activated in adenine-induced CKD rat model, and involved in the renal fibrosis process of CKD.
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Objective:To investigate the value of monitoring on serum silent information regulator-related enzyme 3 (SIRT3), glucagon-like peptide-1 (GLP-1) and angiopoietin-like protein 4 (ANGPTL4) in patients with acute ischemic stroke (AIS).Methods:Eighty patients with AIS who treatment in Qiongzhong Li and Miao Autonomous County People′s Hospital from May 2019 to April 2022 were selected retrospectively as the observation group, and 60 healthy volunteers who underwent physical examination during the same period were selected as the normal control group. The levels of serum SIRT3, GLP-1, and ANGPTL4 between the two groups were compared. The neurological deficit degree of AIS patients was evaluated by National Institutes of Health Stroke Scale(NIHSS) and the correlation of SIRT3, GLP-1 and ANGPTL4 with neurological deficit degree were analyzed. The levels of serum SIRT3, GLP-1 and ANGPTL4 before and after treatment and their difference value were compared between different clinical outcome of AIS patients, the risk factors for poor clinical outcome of AIS patients were analyzed by Logistic regression analysis, the value of prediction was analyzed by receiver operating characteristic (ROC) curve.Results:The level of serum GLP-1 in the observation group was lower than that in the normal control group: (50.37 ± 5.69) nmol/L vs. (34.89 ± 4.26) nmol/L; and the levels of serum SIRT3 and ANGPTL4 in the observation group were higher than those in the normal control group: (50.37 ± 5.69) ng/L vs. (34.89 ± 4.26) ng/L, (15.07 ± 3.12) μg/L vs. (11.15 ± 2.63) μg/L, there were statistical differences ( P<0.05). The results of correlation analysis showed that the levels of serum SIRT3 and ANGPTL4 were positively correlated with the degree of neurological impairment in AIS patients( r = 0.631, 0.776, P<0.05), and the level of serum GLP-1 was negatively correlated with the degree of neurological impairment in AIS patients ( r = - 0.693, P<0.05). After treatment, 66 patients obtained good clinical outcome, the good outcome rate was 82.50%(66/80). The levels of serum SIRT3 and ANGPTL4 in the poor clinical outcome patients were higher than those in the good clinical outcome patients: (41.33 ± 4.74) ng/L vs. (37.82 ± 4.05) ng/L, (12.98 ± 2.17) μg/L vs. (11.69 ± 2.06) μg/L; the level of serum GLP-1 in the poor clinical outcome patients was lower than that in the good clinical outcome patients: (592.33 ± 98.44) nmol/L vs. (709.41 ± 125.31) nmol/L; the difference value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in the poor clinical outcome patients were lower than those in the good clinical outcome patients: (10.22 ± 2.05) ng/L vs. (12.31 ± 2.94) ng/L, (268.21 ± 70.12) nmol/L vs. (379.92 ± 85.33) nmol/L, (2.18 ± 0.65) μg/L vs. (3.36 ± 0.94) μg/L, there were statistical differences ( P<0.05). The results of Logistic regression analysis showed that differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment were all independent influencing factors of poor clinical outcome in patients with AIS ( P<0.05). The results of ROC curve analysis showed that the area under the curve (AUC) of differences value of SIRT3, GLP-1 and ANGPTL4 before and after treatment in predicting poor clinical outcome were 0.701, 0.758 and 0.844, respectively, and had certain predictive value, the AUC of joint evaluation was the largest (0.912). Conclusions:The levels of serum SIRT3 and ANGPTL4 in patients with AIS are increased, and the level of serum GLP-1 is decreased, and they are related to the degree of neurological deficit. Clinical monitoring of their level changes is helpful for clinical evaluation of the clinical outcome of patients with AIS.
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Angiopoietin-like protein 4 (ANGPTL4) is involved in the regulation of glucose and lipid metabolism and angiogenesis, and is closely related to tumorigenesis, development, invasion and metastasis. The abnormal expression of ANGPTL4 gene can promote or inhibit the growth and proliferation of tumor cells and play a tumor-promoting or anti-tumor role in the occurrence and development of tumors. To explore the role of ANGPTL4 gene in the occurrence and development of different tumors can provide reference for evaluating the diagnosis, prognosis and curative effect of tumors.
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@#AIM: To investigate the effects of intravitreal injection of conbercept-assisted vitrectomy(PPV)on proliferative diabetic retinopathy(PDR)and inflammatory factors and angiopoietin-like protein 4(ANGPTL4)in the vitreous. <p>METHODS: Totally 90 patients with PDR(99 eyes)who underwent PPV treatment in our hospital from January to February 2018 were selected as subjects, and were divided into PPV group and IVC/PPV group according to whether intravitreal injection of conbercept(IVC).The surgical indexes of the two groups, the best corrected visual acuity(BCVA, LogMAR)and the incidence of postoperative vitreous hemorrhage(POVCH)were observed within 3mo after surgery were observed. The levels of interleukin-6(IL-6), interleukin-10(IL-10), C-reactive protein(CRP)and other inflammatory factors and ANGPTL4 in the vitreous of the two groups were measured.<p>RESULTS: In the IVC-assisted PPV group, the operation time, intraoperative severe hemorrhage(bleeding with electrocoagulation pen), iatrogenic retinal tears and postoperative silicone oil filling rate were significantly better than those in the PPV group(<i>P</i><0.05). There was no significant difference in BVCA between the two groups(<i>P</i>>0.05). There was no significant difference in BVCA between the two groups(<i>P</i>>0.05). At 1 and 3mo after operation, BCVA decreased significantly in both groups. Visual acuity improved significantly. The BCVA(LogMAR)of the IVC combined with the PPV group was significantly lower than that of the group. Simple PPV group(<i>P</i><0.05). The occurrence of POVCH The rate was significantly decreased(<i>P</i><0.05), the contents of IL-6, IL-10 and CRP in the vitreous were significantly decreased(<i>P</i><0.05), and the content of ANGPTL4 was significantly increased(<i>P</i><0.05).<p>CONCLUSION: Preoperative vitreous injection of conbercept in the treatment of PDR can reduce the occurrence of intraoperative and postoperative complications, promote the recovery of visual acuity, reduce the inflammatory response in the vitreous and increase the content of ANGPTL4.
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STUDY DESIGN: Experimental human study. PURPOSE: To determine whether angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion in FJ synoviocytes. OVERVIEW OF LITERATURE: Mechanical stress-induced synovitis is partially, but significantly, responsible for degenerative and subsequently osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis (LSS). However, the underlying molecular mechanism remains unclear. IL-6 is highly expressed in degenerative FJ synovial tissue and is responsible for local chronic inflammation. ANGPTL2, an inflammatory and mechanically induced mediator, promotes the expression of IL-6 in many cells. METHODS: FJ tissues were harvested from five patients who had undergone lumbar surgery. Immunohistochemistry for ANGPTL2, IL-6, and cell markers was performed in the FJ tissue samples. After cultured synoviocytes from the FJ tissues were subjected to mechanical stress, ANGPTL2 expression and secretion were measured quantitatively using real-time quantitative reverse-transcription–polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA), respectively. Following ANGPTL2 administration in the FJ synoviocytes, anti-nuclear factor-κB (NF-κB) activation was investigated using immunocytochemistry, and IL-6 expression and secretion were assayed quantitatively with or without NF-κB inhibitor. Moreover, we assessed whether ANGPTL2-induced IL-6 modulates leucocyte recruitment in the degenerative process by focusing on the monocyte chemoattractant protein-1 (MCP-1) expression. RESULTS: ANGPTL2 and IL-6 were highly expressed in the hyperplastic FJ synovium samples. ANGPTL2 was co-expressed in both, fibroblast-like and macrophage-like synoviocytes. Further, the expression and secretion of ANGPTL2 in the FJ synoviocytes increased in response to stimulation by mechanical stretching. ANGPTL2 protein promoted the nuclear translocation of NF-κB and induced IL-6 expression and secretion in the FJ synoviocytes. This effect was reversed following treatment with NF-κB inhibitor. Furthermore, ANGPTL2-induced IL-6 upregulated the MCP-1 expression in the FJ synoviocytes. CONCLUSIONS: Mechanical stress-induced ANGPTL2 promotes chronic inflammation in the FJ synovium by activating IL-6 secretion, leading to FJ degeneration and subsequent LSS.
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Humans , Chemokine CCL2 , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Inflammation , Interleukin-6 , Spinal Stenosis , Stress, Mechanical , Synovial Membrane , Synovitis , Zygapophyseal JointABSTRACT
Objective To investigate the influence factors of serum Angptl 2 levels is to explore the relationship between serum Angptl 2 and carotid atherosclerosis (CAS) in patients with type 2 diabetes mellitus (T2DM). Methods 114 cases of T2DM in clinic were selected.According to the results of color doppler ultrasonography,the patients were divided into T2DM with CAS group(T2DM + CAS,n=58)and simple T2DM group(n= 56).56 healthy subjects were selected as normal control (NC)group during the same period.ELISA method was used to detect the level of serum Angptl 2. Results Serum Angptl 2 levels were significantly higher in T2DM + CAS group and T2DM group than in NC group [(69.83 ± 12.07) vs (42.93 ± 10.44)vs (24.26 ± 8.78)ng/ml,P< 0.01].Correlation analysis showed that serum Angptl 2 was positively correlated with age,BMI,SBP,DBP,TC,TG,LDL-C,FPG and HbA1c in T2DM patients (r=0.574,0.325,0.528,0.308,0.396,0.387,0.295,0.536 and 0.601,respectively,P<0.01),and negatively correlated with HDL-C and FIns in T2DM patients (r= -0.248,-0.352,P<0.01).Similarly,multiple regression analysis showed that FIns,and HbA1c were the independent factors of serum Angptl 2 (β= -2.186,2.680,P<0.01). Conclusion Serum Angptl 2 level is closely related to obesity,blood pressure,blood glucose,blood lipid and insulin.Serum Angptl 2 may play an important role in the development of T2DM and carotid atherosclerosis.
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Angiopoietin-like protein (ANGPTL) 4 is involved in the regulation of multiple tumor growth and metabolism pathways and plays a multifunctional role in many aspects of tumorigenesis such as growth,metastasis,apoptosis,angiogenesis and tumor microenvironment.As one of the members of ANGPTL family,it is confirmed that ANGPTL4 both has a tumor-promoting and tumor-inhibiting effect on digestive system neoplasms in recent years.This dual role may be related to its involvement in regulating different tumor signaling pathways.ANGPTL4 is expected to be a new target for diagnosis and treatment of digestive system neoplasms.
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Objective To explore whether Angiopoietin-like protein 3 (ANGPTL3) is involved in podocyte actin rearrangement,and to analyze whether integrin β3 signal pathway is a key in ANGPTL3 inducing actin rearrangement.Methods The cultured podocytes were divided into six groups:wild type,ADR treated,ADR+ Dex,MOCK,ANGPTL3-cDNA,miRNA,and AD +miRNA group.(1) We observed actin cytoskeleton using Invitrogen reagents with confocal microscopy;(2) Actin cytoskeleton after blocking β3 on podocytes was;(3) The expression of total FAK and p-FAK was through Western blotting.Results (1) The wild type podocyte's cytoskeleton is arranged orderly.After ADR treatment,podocyte's actin are rearranged and weaken (P ＜ 0.05).There was no significant difference in actin arrangement between knock-down and MOCK group.In ANGPTL3-cDNA group the podocyte actin was also significantly rearranged;on the contrary,in miRNA +ADR group,the actin rearrangement never obviously happened (P ＜ 0.05).(2) Over-expression of ANGPTL3 podocytes blocked integrin β3 did not happen actin rearrangement.(3) The expression of p-FAK significantly increased in over-expression ANGPTL3 podocytes.Conclusion ANGPTL3 is a key in inducing actin rearrangement.Intergrin β3 maybe a central pathway in ANGPTL3's role with podocytes.
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Objective@#To explore whether Angiopoietin-like protein 3 (ANGPTL3) is involved in podocyte actin rearrangement, and to analyze whether integrin β3 signal pathway is a key in ANGPTL3 inducing actin rearrangement.@*Methods@#The cultured podocytes were divided into six groups: wild type, ADR treated, ADR+Dex, MOCK, ANGPTL3-cDNA, miRNA, and AD+miRNA group. (1) We observed actin cytoskeleton using Invitrogen reagents with confocal microscopy; (2) Actin cytoskeleton after blocking β3 on podocytes was; (3) The expression of total FAK and p-FAK was through Western blotting.@*Results@#(1) The wild type podocyte's cytoskeleton is arranged orderly. After ADR treatment, podocyte's actin are rearranged and weaken (P<0.05). There was no significant difference in actin arrangement between knock-down and MOCK group. In ANGPTL3-cDNA group the podocyte actin was also significantly rearranged; on the contrary, in miRNA+ADR group, the actin rearrangement never obviously happened (P<0.05). (2) Over-expression of ANGPTL3 podocytes blocked integrin β3 did not happen actin rearrangement. (3) The expression of p-FAK significantly increased in over-expression ANGPTL3 podocytes.@*Conclusion@#ANGPTL3 is a key in inducing actin rearrangement. Intergrin β3 maybe a central pathway in ANGPTL3's role with podocytes.
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Objective To detect the serum levels of angiopoietin-like protein 2 (ANGPTL 2) and vascular endothelial growth factor (VEGF) in patients with rheumatoid arthritis (RA),and to analyze their value in the differential diagnosis of RA in order to clarify whether they are synergetic in the pathogenesis of RA.Methods Seventy-seven patients with RA and 25 subjects for heath check-up in the same period were selected.According to the relevant clinical information,the RA patients were divided into three subgroups:high disease activity group [(DAS28)＞5.1],moderate disease activity group (3.2＜DAS28 ≤5.1),low disease activity group (DAS28 ≤3.2).Enzyme-linked immunosorbent assay (ELISA) was used to masure the levls of ANGPTL2 and VEGF of those groups.The data were analyzed by t test,Mann-Whitney U test,Kruskal-Wallis H test and Speraman correlation analysis.Results ① The serum levels of ANGPTL2 and VEGF in RA patients were significantly higher than those in control group [(5.3±1.1) ng/ml vs (3.3±0.9) ng/ml,Z=-6.644;(106±30) pg/ml vs (93±12) pg/ml,Z=-4.4115,P＜0.05].② Serum level of ANGPTL2 in RA patients with high disease activity was higher than low disease group and healthy control group {[5.7(1.3)] ng/ml vs [4.5(0.3)]ng/ml,H=4.257,P＜0.05;[5.7 (1.3)] ng/ml vs [3.3 (0.9)] ng/ml,H=7.639,P＜0.05}.Serum level of VEGF in RA patients with high disease activity was higher than low disease group and healthy control group {[116(37)]pg/ml vs [96(8)] pg/ml,H=3.579,P＜0.05;[116(37)] pg/ml vs [92.90(12.24)] pg/ml,H=5.698,P＜0.05].③ There was a positive correlation between the serum level of ANGPTL2 and DAS28 score,erythrocyte sedimentation rate,swollen joint count and tender joint count (rDAS28=0.703,rESR=0.311,rSJC=0.503,rTJC=0.670,P＜0.05),so was VEGF (rDAS28=0.553,rESR=0.260,rSJC=0.399,rTJC=0.538,P＜0.05).④ In RA patients,there was a positive correlation between ANGPTL2 and VEGF (r=0.853,P＜0.05).Conclusion ANGPTL2 might coordinate with VEGF and be involved in the immune process of RA,and it might be regarded as one of the reference indexes of RA activity,so that it may contribute to access and monitor the condition of RA.
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Objective To measure the serum levels of angiopoietin-like protein (ANGPTL) 3, ANGPTL4 and RANKL in patients with rheumatoid arthritis (RA), and the relationship between ANGPTL3/ANGPTL4 and clinical manifestations were analyzed. Methods Blood samples were drawn from 72 patients with RA and 28 healthy subjects. Serum levels of ANGPTL3, ANGPTL4 and RANKL were tested by enzyme linked immuno-sorbent assay (ELISA). Nonparametric rank sum test was used for the comparisons between groups and Spearmanˊs correlation test was used for correlation analysis. Results ① The serum level of ANGPTL3 was significantly increased in RA group compared to healthy group [800.325(577.477, 1 750.636) pg/ml vs 487.900 (382.340, 565.499) pg/ml, P<0.05, Z=-6.082]. ② The serum level of ANGPTL4 was significantly increased in RA group compared to healthy group [1 036.199(853.347, 1 746.677) pg/ml vs 706.095(558.571, 807.302) pg/ml, Z=-5.962, P<0.05].③ The serum levels of ANGPTL3 and ANGPTL4 in RA patients were increased with the rise of disease activity (DAS 28) [ANGPTL3 in the low disease activity groupwas 457.265 (373.709, 605.296) pg/ml, that of the moderate disease activity group was 785.815(679.156, 1 308.785) pg/ml, that of the high disease activity group was 1 502.038 (817.713, 1 960.493) pg/ml, P<0.05; ANGPTL4 in the low disease activity group was 737.604 (467.040, 918.222) pg/ml, that of the moderate disease activity group was 991.227 (819.456, 1 699.972) pg/ml, and that of the high disease activity group was 1 842.310 (1 252.023, 2 669.902) pg/ml, P<0.05].④ANGPTL3 and ANGPTL4 was positively correlated with RANKL (r=0.554, 0.619, P<0.01).⑤ The serum level of ANGPTL4 was significantly increased in patients with bone destruction, compared to those without bone destruction [1 624.071(949.432, 2 622.371) pg/ml vs 927.590(737.604, 1 409.798) pg/ml, Z=-2.483, P<0.05]. Conclusion The serum levels of ANGPTL3 and ANGPTL4 are increased in RA, and are both positively correlated with disease activity, moreover, ANGPTL4 is associated with pathological bone destruction.
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Objective To explore the expressions and clinical value of angiopoietin like protein 1 (Ang-1)and angiopoietin like protein 2 (Ang-2)in patients with gastric cancer.Methods 65 patients with gastric cancer and 50 healthy subjects for con-trol group were collected from June in 2012 to December in 2014.The level of Ang-1 and Ang-2 were determined by enzyme-linked immunosorbent assay (ELISA).The results were compared.Results Compared with control group (19.8±2.1 μg/L),the level of Ang-1 in patients with gastric cancer (19.8±2.1 μg/L)was no statistics difference (P >0.05),but Ang-2 (2.3±0.8 μg/L)was significantly higher than those of healthy subjects (0.8±0.2 μg/L,t=2.50,P 0.05).The level of Ang-2 in TNM stage Ⅲ~Ⅳ (2.6±0.5 μg/L)was obviously higher than that in stage.Ⅰ~Ⅱ (1.6±0.4 μg/L).Ang-2 levels were signif-icantly higher in patients with lymph node metastasis (2.7±0.5 μg/L)or postoperative recurrence after one year (2.0±0.6μg/L)than those without lymph node metastasis (1.6 ± 0.5 μg/L)or postoperative recurrence (1.2 ± 0.5 μg/L,P <0.05).The level of Ang-2 in gastric cancer was significantly positive correlated with tumor stage and lymph node metastasis (r=0.31 and 0.33 respectively,P <0.01).Conclusion Ang-2 level was significantly increased in gastric cancer.Its level was significantly correlated with tumor stage,lymph node metastasis and prognosis,which has important application value for the cancer progression,clinical observation and prognosis evaluation of gastric cancer.
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Objective To study the assosiation of angiopoietin-like protein 2 (ANGPTL2) to lower extremity arterial disease in type 2 diabetes mellitus.Methods A total of 360 type 2 diabetic patients were divided into three groups:without (group A),with mild to moderate (group B),and severe (group C) lower extremity arterial disease according to the ankle brachial index.And,120 healthy subjects serveed as control group.The levels of ANGPTL2,high sensitivity C-reactive protein (hsCRP),free fatty acid,biochemical index,and fasting insulin were detected.And,waist-to-hip ratio (WHR),body mass index (BMI),insulin resistance index were calculated.Results The level of ANGPTL2 was getting higher and higher as lower extremity arterial disease progressing.The level of ANGPTL2 in group B was higher than that in group A [1.27 (1.09,1.51) vs 0.88 (0.66,1.07) μg/L,P＜0.05],and the level of ANGPTL2 in group C was higher than that in group B [1.70 (1.45,1.91) vs 1.27 (1.09,1.51)μg/L,P＜0.05].Pearson correlation analysis showed that the ANGPTL2 level in serum positively correlated with hsCRP,BMI,WHR,cholesterol,low-density lipoprotein-cholesterol,fasting insulin,and insulin resistance index.Logistic regression analysis showed that the levels of ANGPTL2,hsCRP,and glycosylated hemoglobin were significantly associated with lower extremity arterial disease in type 2 diabetes mellitus.Conclusion It is possible that ANGPTL2 is one of the risk factors of lower extremity arterial disease in type 2 diabetes mellitus,and which is likely to be of great significance in the early prediction,disease assessment,and prognosis evaluation for lower extremity arterial disease in type 2 diabetes mellitus.
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Objective To explore the level of angiopoietin‐like protein 4 (ANGPTL4) in patients with early chronic kidney disease (CKD ) in diabetes and the influence of pioglitazone on the level. Methods 92healthypeoplewithnormalglucosetolerancewereselectedasthecontrols(NCgroup).89 newly diagnosed T2DM were selected (T2DM group ). 90 cases of CKD group were divided into pioglitazone (PGZ) and glimepiride (GLI) treated subgroups ,45 cases in each subgroup. After treatment , serum ANGPTL4 levels were observed in CKD group. Results There were significant differences in serum ANGPTL4 levels among NC ,T2DM and CKD groups [(34.8 ± 4.75) vs (31.1 ± 3.65) vs (27.1 ± 3.52)ng/ml ,P 0.05 ;(99.70 ± 12.80 ) vs (122.40 ± 13.10 )mg/24 h ,P < 0.05]. HbA1 c ,FIns ,UAlb/Cr were the independent related factors influencing ANGPTL4 of CKD patients. Conclusion Serum ANGPTL4 has a lower level in CKD patients. PGZ is effective in treating CKD. This role is associated with the increase of serum ANGPTL4.
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Objective To explore Angptl2(angiopoietin-like protein 2)expression in tumor tis-sue and serum in patients with breast cancer(BC). Methods A total of 78 BC patients were enrolled in this study. Immunohistochemistry was used to detect Angptl2 expression in tumor and adjacent normal tis-sues. Preoperative and postoperative serum Angptl2 levels were determined via ELISA. Correlation among Angptl2 expression,clinicopathological factors and progression-free survival(PFS)were further evalua-ted. The receiver operating characteristics(ROC)curve was constructed to describe diagnostic specificity and sensitivity. Results Angptl2 was positively expressed in 64(82. 1% )cases. The rates of high and moderate expression of Angpt l2 in tumor and adjacent tissues were 53. 8%(42 / 78)and 7. 7%(6 / 78), respectively(P ﹤ 0. 001). Moreover,the elevated Angptl2 protein was significantly associated with lymph metastasis and adverse PFS. In addition,serum Angptl2 level in BC patients was significantly higher than that in benign controls[(218. 72 ± 88. 02)vs(80. 88 ± 30. 59)ng/ ml,P ﹤ 0. 01]. The area under the curve(AUC)was 0. 909,which indicated a good function for diagnosis. Postoperative serum Angptl2 level was decreased to(142. 43 ± 60. 29)ng/ ml,but still higher than that in controls(P ﹤ 0. 01). Conclusion The expression of Angptl2 may increase in tumor tissue and serum of BC and it may be a potential tumor marker for diagnosis and prognosis.
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[Summary] This paper was to investigate whether serum angiopoietin-like protein 2 (Angptl 2) is associated with macrovascular complications in type 2 diabetes mellitus.The results showed that there were statistically significant differences in serum Angptl 2 levels among control group and groups of type 2 diabetic patients with or without carotid atherosclerosis [0.98 (0.82-1.22),3.70 (2.69-4.85),1.17 (0.76-2.47) ng/ml].Logistic regression showed that Angptl 2 was an independent risk factor of macrovascular complications in the patients with type 2 diabetes.
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Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.
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Objective To explore the expression of angiopoietin like protein-1(Ang-1)and angiopoietin like protein-2(Ang-2)in type 2 diabetes mellitus(T2DM)and its relationship with angiopathy.Methods Ang-1,Ang-2,FBG,FINS and HbA1c were meas-ured in 120 cases of T2DM,including 32 cases of macroangiopathy,52 cases of microangiopathy and 36 cases without angiopathy, and 50 healthy subjects with physical examination were selected as the control group.The detection results were compared between the two groups.Results Compared with control group,the Ang-1 level in the T2DM group was no statistical difference(P >0.05), but the Ang-2 level was significantly higher than that in the control group(t=2.6,P 0.05).Conclusion The Ang-2 level in the patients with T2DM is significantly increased,which is closely related with HbA1c and insulin resistance,furthermore Ang-2 may participate in the generation and development of pathogenesis in T2DM.
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Objective To observe the effect of irbesartan on the expression of angiopoietinlike protein 2 (ANGPTL2) in the diabetic rats kidney and explore the underlying mechanism.Methods A total of sixty male SD rats were divided into normal control group (NC group,n=15) and experimental group (n=45) randomly.The experimental group was fed with high sugar-fat diet and given a low dose streptozocin (STZ 30 mg/kg)to establish type 2 diabetic model.Rats successfully induced diabetes were randomly divided into 2 groups:diabetes group (DM) and irbesartan group (DI).Weight,blood pressure,blood glucose,serum creatinine (Scr),blood urea nitrogen(BUN),24 hour urinary albumin(UAL) and renal histomorphology were observed after drug intervention at the 4th,8th and 12thweeks.The expression of ANGPTL2 in renal tissue were detected by immunohistochemistry,real-time PCR and Western blotting.Results The levels of Scr,BUN,TG,TC and UAL in group DM were higher than in group NC at the 4th,8th and 12th week (all P ＜ 0.05).Compared with that in group DM,above indexes were lower in group DI at the 4th,8th and 12th week (all P ＜ 0.05).The pathological changes of the kidney in group DM were more serious than that in group DI.The expression of ANGPTL2 in group DM was much higher than that in group NC at the 4th,8th and 12th week (all P ＜0.05),and irbesartan treatment inhibited the up-regulation of ANGPTL2 in group DI(all P ＜ 0.05).Conclusion The expression of ANGPTL2 increases in T2DM rats kidney tissue with time and irbesartan can inhibit the up-regulation of ANGPTL2 in T2DM rats.
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Background The special pathological change of diabetic retinopathy(DR)is microvascular disorder.Angiopoietin-like protein 2(Ang-2)is a new protein associated with genesis of blood vessels.Quercetin has multiple pharmacological action,including improving the microcircularion and the permeability of blood capillary.However,the action mechanism of Ang-2 on DR was unclear.Objective The present study was to investigate the effects of quercetin on Ang-2 and its receptor Tie2 expression in retina with diabetes mellitus.Methods Sixty clean male Wistar rats were randomized into 7 groups and 10 rats for each group,and 10 rats served as blank control group.Streptozotocin of 35 mg/kg was intraperitoneally injected in 60 rats to establish the diabetic models.Quercetins encapsulated by liposome with the doses of 50,150 and 250 mg/(kg · d)(3-5 ml)were used to gavage in different groups of models for 12 weeks,and normal saline solution and calcium dobesilate were used at the same fashion as the negative control group and positive control group,respectively.Twelve weeks later,the animals were sacrificed and retinas were isolated.Expressions of Ang-2 protein and Tie2 mRNA in retinas were detected by ELISA and RT-PCR,respectively.The usage and rearing of the animals complied with the Regulations for the Administration of Affair Concerning Experimental Animals by State Sciences and Technology Commission.Results ELISA showed that the A450 of Ang-2 in 150 and 250 mg/(kg · d)quercetin groups was 0.796±0.057 and 0.842±0.043 respectively and was lower than that negative group(1.012±0.046),showing statistically significant differences(q =2.95,2.698,P＜0.05).RT-PCR assay showed that expression of Tie2 mRNA(Tie2 mRNA/GAPDH mRNA)in retinas was 0.712±0.092 and 0.821±0.087,presenting statistically significant differences in comparison with negative group(1.182±0.098)(q =3.497,2.852,P＜0.05).The expression levels of Ang-2 and Tie2 mRNA in retina were lowest in 150 mg/(kg · d)quercetin group.Conclusions Quercetin can improve the retinal microcirculation by downregulating the expressions of Ang-2 and its receptor in early period of diabetic rats.