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@#Angiopoietin-like 4(ANGPTL4)is one of the angiopoietin family members and plays a regulatory role in lipid metabolism,glucose homeostasis,inflammatory signal transduction,angiogenesis and vascular permeability.Inflammatory reaction in tumor microenvironment regulates tumor progression,and tumor angiogenesis plays a vital role in tumor growth and metastasis,so ANGPTL4 is closely related to tumor occurrence and development.Many studies have shown that ANGPTL4 plays an important regulatory role in tumor growth,anoikis resistance,tumor angiogenesis and tumor metastasis.This paper reviews the role of ANGPTL4 in tumor progression.
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Objective: To study the preliminary pharmacodynamics effect of Shuiludihuang Capsule on rats with type 2 diabetic nephopathy induced by high-fat and sugar diet combined low dose streptozotocin (STZ), and to investigate its mechanism. Methods: Type 2 diabetic nephropathy animal model was established by feeding with high fat and sugar diet combined with low dose of STZ. The FBS, TC, TG, UMA, kidney weight, the hypertrophy index, etc were measured to study its effects of reducing blood glucose and protecting kidney, and its pharmacodynamic effects were expounded by kidney pathological section. The expressions of Angptl4, Desmin and NF-κB in kidney tissues were tested by immunohistochemistry, The expressions of Angptl4 and Desmin in kidney tissues were tested by western blotting, and APN, LEP and Urine Angptl4 were tested by ELISA to probe into its mechanism tentatively. Results: Compared with the model control group, kidney weight, the hypertrophy index, FBG, TC, TG, LEP and the expressions of Angptl4, Desmin and NF-κB in rats of each group (9, 6 mg/kg) were significantly decreased, and body mass, the serum APN level were significantly increased, with significant difference (P < 0.05, P < 0.01). Conclusion: Shuiludihuang capsule can regulate glucose and fat metabolism, reduce inflammation, reduce Angptl4, Desmin and NF-κB expression levels in renal tissue, improve renal podocyte injury, reduce urinary protein, and delay renal fibrosis and sclerosis. Its mechanism may be related to Angptl4, Desmin and NF-κB pathways.
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Objective To study how ANGPTL4 modulates phenylephrine(PE)-induced cardiac fibrosis. Methods PE was applied to induce cardiac fibrosis. The knockdown effect of ANGPTL4 under PE stimuli was confirmed by Western blot;the proliferation of cardiac fibroblast was detected by CCK-8;mRNA levels of Collagen 1(Col1)and connective tissue growth factor(CTGF)were detected by QPCR to investigate the regula-tion of cardiac fibrosis by ANGPTL4. Results PE induced the proliferation of cardiac fibroblast and the up-regula-tion of mRNA levels of Col1 and CTGF;ANGPTL4 knockdown deteriorated cardiac fibrosis,manifested by the up-regulation of Col1 and CTGF. Conclusion ANGPTL4 inhibits PE-induced cardiac fibrosis.
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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 the influence of buyang huanwu decoction (BYHWD) on the denervated tibial muscle atrophy of rats and to study the mechanisms of BYHWD defering denervated muscle atrophy of rats. METHODS: Sprague-Dawley rats were subjected to common peroneal nerve crush model, then they were randomly divided into sham operation group, model group, BYHWD high-dose, medium-dose, low-dose groups, mecobalamin group (positive control). Each group has ten rats. The gavage lasted for 18 d. After that, performed slice, staining and analysis morphology were performed. The wet weight ratio of tibial muscle was measured. At the same time, qRT-PCR and western-blot detect the differential expression of Angpt14 and PI3K in the high-dose group of BYHWD and model group. RESULTS: (1) Wet weight ratio: BYHWD high and medium-group increased significantly compared with model group (P<0.01 or P<0.05). (2) The motor end-plate: the sham operation group is sepia, oval or round; the BYHWD high-dose group and mecobalamin group has little chage; the BYHWD medium-dose group, low-dose group and the model group has lessen, shape is not rule gradually, the edge is rough, coloring is slight gradually, (3) the expression of Angpl14 and PI3K: compared with model group, the BYHWD high and medium-group increased significantly (P<0.05 or P<0.01). CONCLUSION: BYHWD can effectively delay denervated tibial muscle atrophy of rats by increasing the wel weight ratio and defering the degeneration of the motor end-plate which mechanism maybe increase Angpt14 and PT3K expression.
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BACKGROUND AND OBJECTIVES: Diabetes is reported to reduce the function or number of progenitor cells. We compared the gene expression patterns of bone marrow-derived mesenchymal stem cells from diabetic (DM-BMCs) and healthy (non-DM-BMCs) rats and suggested Angiopoietin-like 4 (Angptl4) could be a responsible factor for impaired angiogenesis of DM-BMCs. SUBJECTS AND METHODS: BMCs were isolated from DM or non-DM rat, and in vitro angiogenesis activity was compared by tube formation assay on Matrigel and complementary deoxyribonucleic acid expression was analyzed by microarray with or without oxytocin treatment. Human BMCs (hBMCs) were treated with high glucose, and were performed polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Angptl4 plasmid DNA and micro ribonucleic acid-132 (miR-132) were transfected to immortalized hBMCs. RESULTS: In vitro angiogenesis assay showed the impaired tube formation in DM-BMCs, and slightly recovery by oxytocin treatment. Angptl4, an adipokine, was upregulated in DM-BMCs compared to non-DM-BMCs. Oxytocin treatment reduced Angptl4 in DM-BMCs. In hBMCs, overexpression of Angptl4 attenuated the tube formation. In addition to Angptl4, miR-132 was increased by high glucose treatment. Collectively, high glucose resulted in impaired tube formation through miR-132 induction and Angptl4 upregulation in BMCs. CONCLUSION: Our results show that the angiogenic activity of BMCs is impaired by high glucose stress, which would be mediated by Angptl4 and miR-132.