Abstract
Angiogenesis is a highly coordinated, extremely complex process orchestrated by multiple signaling molecules and blood flow conditions. While sprouting mode of angiogenesis is very well investigated, the molecular mechanisms underlying intussusception, the second mode of angiogenesis, remain largely unclear. In the current study two molecules involved in vascular growth and differentiation, namely endoglin (ENG/CD105) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) were examined to unravel their specific roles in angiogenesis. Down- respectively up-regulation of both molecules tightly correlates with intussusceptive microvascular growth. Upon ENG inhibition in chicken embryo model, formation of irregular capillary meshwork accompanied by increased expression of COUP-TFII could be observed. This dynamic expression pattern of ENG and COUP-TFII during vascular development and remodeling correlated with formation of pillars and progression of intussusceptive angiogenesis. Similar findings could be observed in mammalian model of acute rat Thy1.1 glomerulonephritis, which was induced by intravenous injection of anti-Thy1 antibody and has shown upregulation of COUP-TFII in initial phase of intussusception, while ENG expression was not disturbed compared to the controls but decreased over the time of pillar formation. In this study, we have shown that ENG inhibition and at the same time up-regulation of COUP-TFII expression promotes intussusceptive angiogenesis.
Highlights
Intussusception is a mechanism of vascular growth that is supplemental to the process of sprouting angiogenesis
Numerous studies have demonstrated the involvement of the transforming growth factor beta (TGFβ), its receptors, for example Endoglin, (ENG) and members of the Notch receptor family play a key role in pathogenesis of glomerular diseases [9,10,11,12]
We show that ENG inhibition influences expression of the chicken ovalbumin upstream promoter transcription factor and promotes intussusceptive angiogenesis
Summary
Intussusception is a mechanism of vascular growth that is supplemental to the process of sprouting angiogenesis. This process allows rapid expansion of incipient capillary plexuses and plays an important role in vascular remodeling under normal and pathological conditions. On the other hand studies with inhibition of VEGF-signaling proved that intussusceptive vascular growth, expansion and remodeling occur mainly in a VEGF-independent manner [4,5,6]. Numerous studies have demonstrated the involvement of the transforming growth factor beta (TGFβ), its receptors, for example Endoglin, (ENG) and members of the Notch receptor family play a key role in pathogenesis of glomerular diseases [9,10,11,12]
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