Microvascular Endothelial Cells Differ in Basal and Hypoxia-Regulated Expression of Angiogenic Factors and Their Receptors

Tscheudschilsuren, Gerelsul; Aust, Gabriela; Nieber, K; Schilling, Nicole; Spanel‐Borowski, Katharina

doi:10.1006/mvre.2001.2346

Cited by 29 publications

(24 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1B). Purified CLENDO cells did not express cytokeratin 18, consistent with previous reports that demonstrated that the majority of luteal microvascular endothelial cells do not express cytokeratin 18 (Ricken et al, 1995;Tscheudschilsuren et al, 2002) (Fig. 1B).…”

Section: Characterization Of Clendo Cellssupporting

confidence: 91%

TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum

Maroni

Davis

2011

Journal of Cell Science

View full text Add to dashboard Cite

SummaryCyclical formation and regression of the ovarian corpus luteum is required for reproduction. During luteal regression, the microvasculature of the corpus luteum is extensively disrupted. Prostaglandin F2, a primary signal for luteal regression, induces the expression of transforming growth factor 1 (TGFB1) in the corpus luteum. This study determined the actions of TGFB1 on microvascular endothelial cells isolated from the bovine corpus luteum (CLENDO cells). We hypothesized that TGFB1 participates in the disruption of the microvasculature during luteal regression. TGFB1 activated the canonical SMAD signaling pathway in CLENDO cells. TGFB1 (1 ng/ml) significantly reduced both basal and fetal-calf-serum-stimulated DNA synthesis, without reducing cell viability. TGFB1 also significantly reduced CLENDO cell transwell migration and disrupted the formation of capillary-like structures when CLENDO cells were plated on Matrigel. By contrast, CLENDO cells plated on fibrillar collagen I gels did not form capillary-like structures and TGFB1 induced cell death. Additionally, TGFB1 caused loss of VE-cadherin from cellular junctions and loss of cellcell contacts, and increased the permeability of confluent CLENDO cell monolayers. These studies demonstrate that TGFB1 acts directly on CLENDO cells to limit endothelial cell function and suggest that TGFB1 might act in the disassembly of capillaries observed during luteal regression.

show abstract

Section: Characterization Of Clendo Cellssupporting

confidence: 91%

TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum

Maroni

Davis

2011

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Furthermore, hypoxia-inducing factor-1 modulates the expression of ANG-1 and ANG-2 in a cell type -specific manner, whereby ANG-2 expression was induced in endothelial cells but suppressed in smooth muscle cells, whereas ANG-1 levels were unaffected in both cell types (113). Moreover, only a subset of endothelial cells is responsive to hypoxia induction of ANG-2 (114). Therefore, failure of signal transduction from TIE-2 receptors in different populations of endothelial cells may account for the observed discrepancies in the action of ANG-1 and ANG-2 (48,115).…”

Section: Dr Jekyll and Mr Hyde In Tumor Angiogenesismentioning

confidence: 99%

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

Shim

Wong

2007

Molecular Cancer Research

152

111

View full text Add to dashboard Cite

Angiopoietins (ANG-1 and ANG-2) and their TIE-2 receptor tyrosine kinase have wide-ranging effects on tumor malignancy that includes angiogenesis, inflammation, and vascular extravasation. These multifaceted pathways present a valuable opportunity in developing novel inhibition strategies for cancer treatment. However, the regulatory role of ANG-1 and ANG-2 in tumor angiogenesis remains controversial. There is a complex interplay between complementary yet conflicting roles of both the ANGs in shaping the outcome of angiogenesis. Embryonic vascular development suggests that ANG-1 is crucial in engaging interaction between endothelial and perivascular cells. However, recruitment of perivascular cells by ANG-1 has recently been implicated in its antiangiogenic effect on tumor growth. It is becoming clear that TIE-2 signaling may function in a paracrine and autocrine manner directly on tumor cells because the receptor has been increasingly found in tumor cells. In addition, A 5 B 1 and A v B 5 integrins were recently recognized as functional receptors for ANG-1 and ANG-2. Therefore, both the ligands may have wide-ranging functions in cellular activities that affect overall tumor development. Collectively, these TIE-2 -dependent and TIE-2 -independent activities may account for the conflicting findings of ANG-1 and ANG-2 in tumor angiogenesis. These uncertainties have impeded development of a clear strategy to target this important angiogenic pathway. A better understanding of the molecular basis of ANG-1 and ANG-2 activity in the pathophysiologic regulation of angiogenesis may set the stage for novel therapy targeting this pathway. (Mol Cancer Res 2007;5(7):655 -65)

show abstract

“…ARNT expression is not affected by oxygen concentration, whereas HIF1A is rapidly ubiquitinated under hypoxia, which targets the protein for degradation by the proteasome [12][13][14]. In bovine CL, HIF1 expression has been reported only in cultured bovine luteal endothelial cells [15] and steroidogenic cells [16]. However, since the expression of HIF1 in bovine CL during the estrous cycle has not been determined, it is unclear whether HIF1 participates in regulating luteal angiogenesis during the estrous cycle in cattle.…”

mentioning

confidence: 99%

Hypoxia is Important for Establishing Vascularization During Corpus Luteum Formation in Cattle

2010

View full text Add to dashboard Cite

Abstract. Hypoxia-inducible factor 1 (HIF1) has been demonstrated to have critical roles in angiogenesis via transcriptional regulation of angiogenic factors, such as vascular endothelial growth factor (VEGF). In the ovary, angiogenesis is known to occur after ovulation in the developing corpus luteum (CL) in mammals. To determine whether HIF1 participates in angiogenesis in bovine CL, the present study investigated the mRNA and protein expressions of the HIF1 alpha subunit (HIF1A) and VEGF in bovine CL during the estrous cycle. The effects of hypoxia on the expressions of HIF1A protein, VEGF mRNA and VEGF protein in bovine luteal cells were also examined by using a cell culture system. HIF1A mRNA expression was less at the regressed stage than at the other stages, whereas protein expression of HIF1A was highest at the early luteal stage and decreased thereafter. VEGF mRNA expression was highest at the developing luteal stage and decreased thereafter. VEGF protein expression was highest at the early luteal stage and decreased significantly at the regressed luteal stage. Hypoxia increased the amounts of HIF1A protein, VEGF mRNA and VEGF protein in cultured bovine luteal cells. Furthermore, we found that hypoxia inhibited progesterone production in the mid luteal cells, but not in the early luteal cells. The overall findings indicate that HIF1 is one of the factors promoting VEGF-induced angiogenesis during luteal development, and suggest that the hypoxic conditions formed after follicle rupture contribute to establishing luteal vascularization in cattle. Key words: Cattle, Corpus luteum, Hypoxia, Hypoxia-inducible factor 1, Vascular endothelial growth factor (J. Reprod. Dev. 56: [110][111][112][113][114][115][116] 2010) he corpus luteum (CL) is an organ that is temporarily formed and regressed during the female reproductive cycle. It is formed from a ruptured follicle after ovulation with rapid angiogenesis [1][2][3]. Angiogenesis is known to be stimulated by a variety of growth factors [1,2,4], one of the strongest which is vascular endothelial growth factor (VEGF) [5]. VEGF also has a role in the angiogenesis of newly formed CL in cattle [6,7]. Another factor, hypoxia-inducible factor 1 (HIF1), is a strong inducer of the transcription of erythropoietin [8] and VEGF [9]. A ruptured follicle just after ovulation is thought to be under hypoxic conditions because of bleeding and because it has an immature vasculature [10]. Therefore, we hypothesized that hypoxic conditions are important for establishing the vascular system during luteal development.HIF1 is an obligatory heterodimeric protein composed of two members of the basic-helix-loop-helix (bHLH)-containing PER-ARNT-SIM (PAS) domain family, HIF1A and the aryl hydrocarbon receptor nuclear translocator (ARNT) [11]. ARNT expression is not affected by oxygen concentration, whereas HIF1A is rapidly ubiquitinated under hypoxia, which targets the protein for degradation by the proteasome [12][13][14]. In bovine CL, HIF1 expression has been reported only in culture...

show abstract

Microvascular Endothelial Cells Differ in Basal and Hypoxia-Regulated Expression of Angiogenic Factors and Their Receptors

Cited by 29 publications

References 34 publications

TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum

TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

Hypoxia is Important for Establishing Vascularization During Corpus Luteum Formation in Cattle

Contact Info

Product

Resources

About