Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney

Simon, Matthias; Gröne, Hermann–Josef; Jöhren, Olaf; Kullmer, Johannes; Plate, Karl H.; Risau, Werner; Fuchs, Eberhard

doi:10.1152/ajprenal.1995.268.2.f240

Cited by 200 publications

(236 citation statements)

References 27 publications

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“…Localization of VEGFR-3 in endothelium of gastrointestinal mucosa is in line with expression of VEGF-C mRNA that was found in small intestine (Joukov et al 1996). Our observations are also in line with expression patterns of mRNA of VEGFR-1 and -2 in endothelial cells of adult choroid plexus and kidney glomeruli (Millauer et al 1993;Simon et al 1995).…”

Section: Discussionsupporting

confidence: 89%

Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia

Witmer

Dai

Weich³

et al. 2002

J Histochem Cytochem.

140

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The vascular endothelial growth factor (VEGF) family is involved in angiogenesis, and therefore VEGFs are considered as targets for anti-angiogenic therapeutic strategies against cancer. However, the physiological functions of VEGFs in quiescent tissues are unclear and may interfere with such systemic therapies. In pathological conditions, increased levels of expression of the VEGF receptors VEGFR-1, VEGFR-2, and VEGFR-3 accompany VEGF activity. In this study we investigated normal human and monkey tissues for expression patterns of these receptors. Immunohistochemical staining methods at the light and electron microscopic level were applied to normal human and monkey tissue samples, using monoclonal antibodies (MAbs) against the three VEGFRs and anti-endothelial MAbs PAL-E and anti-CD31 to identify blood and lymph vessels. In human and monkey, similar distribution patterns of the three VEGFRs were found. Co-expression of VEGFR-1, −2, and −3 was observed in microvessels adjacent to epithelia in the eye, gastrointestinal mucosa, liver, kidney, and hair follicles, which is in line with the reported preferential expression of VEGF-A in some of these epithelia. VEGFR-1, −2, and −3 expression was also observed in blood vessels and sinusoids of lymphoid tissues. Furthermore, VEGFR-1, but not VEGFR-2 and −3, was present in microvessels in brain and retina. Electron microscopy showed that VEGFR-1 expression was restricted to pericytes and VEGFR-2 to endothelial cells in normal vasculature of tonsils. These findings indicate that VEGFRs have specific distribution patterns in normal tissues, suggesting physiological functions of VEGFs that may be disturbed by systemic anti-VEGF therapy. One of these functions may be involvement of VEGF in paracrine relations between epithelia and adjacent capillaries.

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Section: Discussionsupporting

confidence: 89%

Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia

Witmer

Dai

Weich³

et al. 2002

J Histochem Cytochem.

140

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“…24 PlGF is derived entirely from the circulating blood and not from the cells of the kidney itself (glomerular podocytes and tubular cells) as urinary VEGF. 25,26 Although no relationship between PlGF and serum creatinine concentrations was found in CHRI patients, serum PlGF levels tended to correlate with diuresis in CHRI and HD patients.…”

Section: Discussionmentioning

confidence: 97%

Placental Growth Factor in Patients with Decreased Renal Function

et al. 2011

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Background: Patients with decreased renal function are characterized by high cardiovascular morbidity and mortality due to complications of premature atherosclerosis. Placental growth factor (PlGF) is a proatherogenic cytokine and new biomarker of cardiovascular events. The aim of this study was to determine PlGF levels and describe their relationship to renal function and risk factors of atherogenesis in patients with decreased renal function. Methods: The study group consisted of 114 subjects: 45 patients with various degrees of decreased renal function (CHRI), 31 longterm hemodialysis (HD) patients, and 38 age-matched healthy control subjects. PlGF was assessed immunochemically (enzyme-linked immunosorbent assay) and routine biochemical parameters were measured using standard laboratory methods. Results: PlGF levels were significantly increased in CHRI and HD patients compared to controls (10.5 ± 3.3 pg/mL in CHRI patients and 11.5 ± 3.4 pg/mL HD patients vs. 8.1 ± 1.8 pg/mL in controls, both p < 0.0001). In CHRI patients, PlGF was detectable in the urine, and its urine concentration correlated with its serum levels. In HD patients, PlGF correlated with low-density lipoproteins (r = 0.36, p < 0.05), but was not related to C-reactive protein levels. Higher levels of PlGF were found in CHRI patients with cardiovascular disease, compared with those free of such complication. Conclusions: PlGF levels are increased in patients with decreased kidney function. PlGF is detectable in the urine, and serum and urine levels of PlGF are significantly interrelated. It is higher in CHRI patients with cardiovascular disease. Further studies are required to demonstrate the usefulness and significance of PlGF in patients with chronic kidney disease.

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“…So far VEGF expression in normal human and rat kidney has been known to be confined to podocytes and distal and collecting duct epithelium (10,18). GEC have been identified as the site of constitutive production of VEGF (19).…”

Section: Discussionmentioning

confidence: 99%

VEGF Expression in Hypoxia and Hyperglycemia

Kim

Chen

Weinstein

et al. 2002

Journal of the American Society of Nephrology

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ABSTRACT. Vascular endothelial growth factor (VEGF), an angiogenic factor for endothelial cells, is produced by glomerular and tubular epithelia. Using immunoelectron microscopy, VEGF expression by podocytes (GEC) and the proximal tubular epithelium of rat kidney was confirmed. To elucidate the mechanisms of VEGF production and its physiologic consequences, studies were performed in cultured GEC and proximal tubular epithelial cells (RPTEC). Both GEC and RPTEC expressed VEGF-120 and 164 mRNA, as detected by quantitative RT-PCR. Hypoxia resulted in an increase in mRNA abundance, more robust in RPTEC than in GEC, and an increase in VEGF expression by 1.9- and 1.6-fold, respectively. 30 mM d-glucose, but not 30 mM l-glucose, resulted in the elevation of VEGF mRNA in RPTEC, but not in GEC, although both cell types showed a comparable modest increase in VEGF expression. Combined treatment (hypoxia and 30 mM d-glucose) resulted in an increase of VEGF mRNA only in RPTEC; however, an enhanced protein expression was detectable in both cell types. To investigate the role of VEGF in branching angiogenesis, “sandwich” co-cultures were applied with endothelial cells and capillary tube formation was compared under the above conditions. Both RPTEC and GEC induced VEGF-dependent capillary tube formation by co-cultured endothelial cells and in both cell types hypoxia further augmented angiogenesis. In contrast, 30 mM d-glucose suppressed angiogenesis in co-cultures with both cell types despite increased mRNA for VEGF receptors 1 and 2. This study shows (1) that VEGF produced by GEC and RPTEC is necessary for branching angiogenesis and (2) that hypoxic environment stimulates VEGF production by both epithelial cell types and augments branching angiogenesis, whereas (3) hyperglycemic microenvironment, although also stimulatory for VEGF production, fails to augment angiogenesis.

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Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney

Cited by 200 publications

References 27 publications

Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia

Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia

Placental Growth Factor in Patients with Decreased Renal Function

VEGF Expression in Hypoxia and Hyperglycemia

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