BACKGROUND: The Angiopoietin-1 (Ang1), Angiopoietin-2 (Ang2) and Tie2 have essential role in angiogenesis in development. Ang1 and Ang2 are ligands which binds to their receptor, Tie2. METHODS: Expression of these proteins was sought during mouse kidney maturation from embryonic day 16 (E16) to 28 days postnatal (P28). RESULTS: Using RNase protection assay and Western blot, these three molecules were expressed throughout the experimental period with peak levels at P28 (Ang1), P14 (Ang2) and P7 (Tie2). By immunohistochemical analysis, Ang1 protein was found to localize to condensing renal mesenchymal cells, and tubules. Ang2 proteins were detected in differentiating outer medullary tubules and the vasa recta bundle area. Tie2 protein was detected in a portion of glomerular tufts and cortical interstitium, and medulla including vessels in the vasa recta. CONCLUSIONS: These data suggest that Ang1, Ang2 and Tie2 proteins are expressed in renal development.
Angiopoietin-1* ; Angiopoietin-2* ; Animals ; Blotting, Western ; Kidney* ; Ligands ; Mice* ; Receptor, TIE-2 ; Ribonucleases

Angiopoietins(ANGPT) and their endothelial cell-specific tyrosine kinase receptors TEK are the major regulators of blood vessels angiogenesis under physiological and pathologic conditions. ANGPT1 is essentially involved in maturation, stabilization, and remodeling of blood vessels through inducing TEK autophosphorylation, promoting endothelial cell migration and survival. Instead, ANGPT2 appears to act as a natural antagonist of ANGPT1, it can activate vascular remodeling with the presence of vascular endothelial growth factor(VEGF) or regress frank blood vessels under the absence of VEGF. High expression of angiopoietins and TEK is often detected in tumor tissues. Many studies showed that disrupting the ANGPT/TEK receptor pathway could inhibit the growth of a number of murine tumors and human tumors. Thus, it is possible that inhibitors targeting the ANGPT/TEK pathway will have broad clinical utility to treatment of cancer.
Angiopoietin-1 ; physiology ; Angiopoietin-2 ; physiology ; Angiopoietins ; physiology ; Humans ; Neovascularization, Physiologic ; physiology ; Receptor, TIE-2 ; physiology

OBJECTIVETo study the expression of angiopoietin-1 (Ang-1) and its receptor Tie-2 in multiple myeloma (MM) patients and RPMI8226 cells, and analyze the significance of Ang-1 expression and its relevance to the tumorigenes and development of MM.

METHODSRT-PCR and Western blot were used to detect the expression of Ang-1 and Tie-2 in bone marrow (BM) samples from 112 MM patients and 24 control subjects, and in RPMI8226 cells. The expression levels of Ang-1 in different groups and disease stages were analyzed.

RESULTSThe positive rate and expression level of Ang-1 were significantly higher in MM group than in control group (P < 0.05). The positive rates of Ang-1 were not significantly different between newly diagnosed and relapsed/refractory MM groups, but its expression level was significantly higher in the latter group than in the former group (P < 0.05). Tie-2 was detected only in 12 MM patients and did not in control group and RPMI8226 cells. Microvessel density in BM samples were significantly higher in MM group than in control group (25.21 ± 0.80 vs 5.23 ± 0.20, P < 0.01), and were higher in Ang-1-positive MM group than in Ang-1-negative MM group (32.98 ± 1.70 vs 16.55 ± 1.30, P < 0.05). The positive rates of Ang-1 protein were not significantly different between stage II and stage III MM (52.1% vs 60.9%, P > 0.05), but the expression level of Ang-1 protein was higher in stage III than that in stage II MM (0.40 ± 0.07 vs 0.22 ± 0.04, P < 0.05). In the newly diagnosed MM patients, the positive rate of Ang-1 protein in PD patients was significantly higher than in PR and MR patients (70.0% vs 19.1%, P < 0.01).

CONCLUSIONHigh expression of Ang-1 is found in MM patients and RPMI8226 cells, and its expression is associated with the disease stage, prognosis and targeted therapy of MM.

Angiopoietin-1 ; Humans ; Multiple Myeloma ; metabolism ; Prognosis ; RNA, Messenger ; Receptor, TIE-2

PURPOSE: Angiopoietin-1 (Ang-1) plays a crucial role in vascular and hematopoietic development, mainly through its cognate receptor, Tie-2. Increased levels of Ang-2 have been shown to be correlated with abnormal tumor angiogenesis in several malignancies. Hence, we estimated the increased expression of Ang-2 relative to Ang-1 in patients with colorectal cancer and correlated our finding with prognosis in order to investigate the relationships between the expressions of Ang-1/Ang-2/Tie-2 receptor and the clinical parameters or overall survival of such patients. METHODS: We retrospectively analyzed 114 tissue samples from patients with colorectal cancer by using immunohistochemistry (IHC) to examine Ang-1, Ang-2, and Tie-2 expressions and to investigate the relationship between those expressions and clinical parameters or overall survival of such patients. A Western blot analysis was used for Ang-2 expression. RESULTS: IHC staining showed a link between Ang-1 and Tie-2 (P = 0.018), as well as meaningful correlations between Ang-2 and Tie-2 receptor (P = 0.022) and between lymph-node metastasis and Ang-2 (P = 0.025). The stronger the IHC staining for Ang-2 expression was, the shorter the cumulative survival was (P = 0.016). CONCLUSION: A relationship was found to exist between Ang-2 and Tie-2 expressions. The Ang-2 was correlated with lymph-node metastasis, and high expression of Ang-2 was indicative of poor overall survival. These findings suggest that Ang-2 is a useful prognostic marker in the management of patients with colorectal cancer. In addition, we suggest that Ang/Tie-2 signaling plays an important role in the progression of colorectal cancer.
Angiopoietin-1* ; Angiopoietin-2* ; Angiopoietins ; Blotting, Western ; Colorectal Neoplasms* ; Humans ; Immunohistochemistry ; Neoplasm Metastasis ; Prognosis ; Receptor, TIE-2* ; Retrospective Studies

OBJECTIVETo investigate the relationship of angiogenesis and the Ang family members/ receptor (Ang/Tie2) in hemangioma.

METHODSExpression of Ang1, Ang2 and the receptor Tie2 was detected with immunohistochemical SP method and RT-PCR method in 17 cases of proliferating hemangioma, 13 involuting cases and 10 cases of normal children skin.

RESULTSThe expression of Ang2 and Tie2 was higher markedly in proliferating hemangiomas than in involuting hemangiomas (P < 0.01), and was rare or negative in normal skin. Expression of Ang1 was rare or negative both in hemangioma and normal skin without significant difference between them (P > 0.05).

CONCLUSIONAng/Tie2 system may play an important role in the proliferating and involuting process of hemangioma.

Angiopoietin-1 ; metabolism ; Angiopoietin-2 ; metabolism ; Child, Preschool ; Hemangioma ; metabolism ; pathology ; Humans ; Infant ; Receptor, TIE-2 ; metabolism

Endothelial cells that form the inner layers of both blood and lymphatic vessels are important components of the vascular system and are involved in the pathogenesis of vascular and lymphatic diseases. Angiopoietin (Ang)-Tie axis in endothelial cells is the second endothelium-specific ligand-receptor signaling system necessary for embryonic cardiovascular and lymphatic development in addition to the vascular endothelial growth factor receptor pathway. The Ang-Tie axis also maintains vascular homeostasis by regulating postnatal angiogenesis, vessel remodeling, vascular permeability, and inflammation. Therefore, the dysfunction of this system leads to many vascular and lymphatic diseases. In light of the recent advances on the role of the Ang-Tie axis in vascular and lymphatic system-related diseases, this review summarizes the functions of the Ang-Tie axis in inflammation-induced vascular permeability, vascular remodeling, ocular angiogenesis, shear stress response, atherosclerosis, tumor angiogenesis, and metastasis. Moreover, this review summarizes the relevant therapeutic antibodies, recombinant proteins, and small molecular drugs associated with the Ang-Tie axis.
Angiopoietins ; Endothelial Cells/metabolism* ; Humans ; Lymphatic Diseases ; Lymphatic System/metabolism* ; Receptor, TIE-2/metabolism* ; Signal Transduction ; Vascular Endothelial Growth Factor A

PURPOSE: It has been reported that angiopoietins and Tie-2 receptor play an important role in the maintenance of glomerular filtration barrier in various glomerulonephritis models. We studied the role of angiopoietins on renal injury in diabetes. METHODS: In this study, we examined the changes of angiopoietin-1, angiopoietin-2, Tie-2 receptor, and nephrin expression in the experimental diabetic nephropathy and also determined whether these changes were modified by renoprotective intervention by angiotensin II receptor blocker, alpha-lipoic acid, and peroxisome proliferator activated receptor (PPAR)-agonist. RESULTS: A marked increase in urinary albumin excretion and glomerular volume was observed in diabetic rats. Renal angiopoietin-2 and Tie-2 receptor expression were significantly higher in diabetic rats than in the control groups, with a significant reduction in renal angiopoietin-2 expression, albuminuria, and renal hypertrophy in angiotensin II receptor blocker-treated diabetic rats. And there was a significant reduction in renal Tie-2 expression and renal hypertrophy in alpha-lipoic acid-treated and PPAR-gamma agonist-treated diabetic rats. CONCLUSION: These results demonstrate that the dysregulation of angiopoietins and Tie-2 receptor can lead to renal hypertrophy and albuminuria. Angiotensin II receptor blocker, alpha-lipoic acid, and PPAR-gamma agonist attenuated these changes in angiopoietins and/or Tie-2 expression and prevented the development of albuminuria and renal hypertrophy in vivo.
Albuminuria ; Angiopoietin-1 ; Angiopoietin-2 ; Angiopoietins* ; Animals ; Diabetic Nephropathies* ; Glomerular Filtration Barrier ; Glomerulonephritis ; Hypertrophy ; Peroxisomes ; Rats ; Receptor, TIE-2 ; Receptors, Angiotensin ; Thioctic Acid

CTHRC1 (collagen triple-helix repeat-containing 1), a protein secreted during the tissue-repair process, is highly expressed in several malignant tumors, including pancreatic cancer. We recently showed that CTHRC1 has an important role in the progression and metastasis of pancreatic cancer. Although CTHRC1 secretion affects tumor cells, how it promotes tumorigenesis in the context of the microenvironment is largely unknown. Here we identified a novel role of CTHRC1 as a potent endothelial activator that promotes angiogenesis by recruiting bone marrow-derived cells to the tumor microenvironment during tumorigenesis. Recombinant CTHRC1 (rCTHRC1) enhanced endothelial cell (EC) proliferation, migration and capillary-like tube formation, which was consistent with the observed increases in neovascularization in vivo. Moreover, rCTHRC1 upregulated angiopoietin-2 (Ang-2), a Tie2 receptor ligand, through ERK-dependent activation of AP-1 in ECs, resulting in recruitment of Tie2-expressing monocytes (TEMs) to CTHRC1-overexpressing tumor tissues. Treatment with a CTHRC1-neutralizing antibody-abrogated Ang-2 expression in the ECs in vitro. Moreover, administration of a CTHRC1-neutralizing antibody to a xenograft mouse model reduced the tumor burden and infiltration of TEMs in the tumor tissues, indicating that blocking the CTHRC1/Ang-2/TEM axis during angiogenesis inhibits tumorigenesis. Collectively, our findings support the hypothesis that CTHRC1 induction of the Ang-2/Tie2 axis mediates the recruitment of TEMs, which are important for tumorigenesis and can be targeted to achieve effective antitumor responses in pancreatic cancers.
Angiopoietin-2 ; Animals ; Carcinogenesis ; Endothelial Cells ; Heterografts ; In Vitro Techniques ; Mice ; Monocytes* ; Neoplasm Metastasis ; Pancreatic Neoplasms ; Receptor, TIE-2 ; Transcription Factor AP-1 ; Tumor Burden ; Tumor Microenvironment

Angiopoietin-1 ; chemistry ; physiology ; Angiopoietin-2 ; chemistry ; physiology ; Angiopoietins ; physiology ; Animals ; Cardiovascular Diseases ; therapy ; Embryonic and Fetal Development ; Humans ; Neoplasms ; blood supply ; Receptor, TIE-2 ; chemistry ; physiology ; Signal Transduction

OBJECTIVE: To investigate the relationship between the expression of Ang2, Tie2 and the angiogenesis of hepatocellular carcinoma in rats. METHODS: Thirty-eight healthy male rats were randomly divided into 3 groups: 5 rats in the control group; 25 rats in the experimental group were equally divided into 5-day, 10-day, 15-day, 20-day, and 25-day groups; the other 8 rats were used as the supplement of the experimental group. An allogenic transplanted rat model of CBRH-7919 hepatocellular carcinoma in situ was established by immunosuppression. The expressions of Ang2 and Tie2 were detected by immunohistochemical staining in cancerous tissues of different developmental stages and liver tissues of the control group. At the same time, microvessel density was determined by anti-CD31 immunohistochemical staining. RESULTS: CBRH-7919 hepatocellular carcinoma models were successfully set up in 24 rats. The expression level of Ang2 and Tie2 in cancerous tissues was much higher than that of liver tissues of the control group (P <0.05). The overexpression of Ang2 was pristine and continuous in different developmental stages. The expressions of Ang2 and Tie2 positively correlated with microvessal density in hepatocellular carcinoma (P<0.05). CONCLUSION The up-regulation of Ang2 and Tie2 may play important roles in the angiogenesis of hepatocellular carcinoma. Ang2 may participate in the start of angiogenesis of hepatocellular carcinoma.
Angiopoietin-2 ; biosynthesis ; genetics ; Animals ; Liver Neoplasms, Experimental ; blood supply ; metabolism ; Male ; Neovascularization, Pathologic ; RNA, Messenger ; genetics ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, TIE-2 ; biosynthesis ; genetics