Impaired angiogenesis in the aging kidney: Vascular endothelial growth factor and thrombospondin-1 in renal disease

Kang, Duk‐Hee; Anderson, Sharon; Kim, Yoon-Goo; Mazzalli, Marilda; Suga, Shin-ichi; Jefferson, J. Ashley; Gordon, Katherine; Oyama, T; Hughes, Jeremy; Hugo, Christian; Kerjaschki, D; Schreiner, George F.; Johnson, Richard J.

doi:10.1016/s0272-6386(01)80019-6

Cited by 158 publications

(211 citation statements)

References 28 publications

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“…Nonetheless, it is possible that endothelial cell-derived gelatinases synergistically act as potent enhancers of tubulogenesis, as well as of tubular recovery after injury. It is thought that the potential for tubular recovery after injury declines in the elderly, and it has been reported that the peritubular capillary area surrounding renal tubules decreases with aging (12,31). Protein array revealed that the expression levels of MMPs in HUVEC were negatively associated with their passage number (unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Enhancement of in vitro human tubulogenesis by endothelial cell-derived factors: implications for in vivo tubular regeneration after injury

Miya¹,

Maeshima²,

Mishima³

et al. 2011

American Journal of Physiology-Renal Physiology

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Section: Discussionmentioning

confidence: 99%

Enhancement of in vitro human tubulogenesis by endothelial cell-derived factors: implications for in vivo tubular regeneration after injury

Miya¹,

Maeshima²,

Mishima³

et al. 2011

American Journal of Physiology-Renal Physiology

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“…For immunostaining with FLAG and ED1, sections were first stained with ED1 using Ni-DAB, then stripped with glycine-HCl (0.1 mol/L, pH 2.2) for 2 hours with constant stirring and finally reprobed with anti-FLAG antibody. The correlation between hypoxic areas and the number of ED-1-positive cells was obtained by computer image analysis, as previously described, 20 under ϫ400 magnification. Pictures were taken at three consecutive fields per specimen (RK, 4 weeks, n ϭ 8) and the percentage of hypoxic (FLAG-positive) tubular cells was calculated.…”

Section: Histopathology and Immunohistochemistrymentioning

confidence: 99%

Hypoxia in Renal Disease with Proteinuria and/or Glomerular Hypertension

Tanaka

Miyata

Inagi

et al. 2004

The American Journal of Pathology

101

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Despite the increasing need to identify and quantify tissue oxygenation at the cellular level, relatively few methods have been available. In this study, we developed a new hypoxia-responsive reporter vector using a hypoxia-responsive element of the 5 vascular endothelial growth factor untranslated region and generated a novel hypoxia-sensing transgenic rat. We then applied this animal model to the detection of tubulointerstitial hypoxia in the diseased kidney. With this model, we were able to identify diffuse cortical hypoxia in the puromycin aminonucleosideinduced nephrotic syndrome and focal and segmental hypoxia in the remnant kidney model. Expression of the hypoxia-responsive transgene increased throughout the observation period, reaching 2.2-fold at 2 weeks in the puromycin aminonucleoside model and 2.6-fold at 4 weeks in the remnant kidney model, whereas that of vascular endothelial growth factor showed a mild decrease, reflecting distinct behaviors of the two genes. The degree of hypoxia showed a positive correlation with microscopic tubulointerstitial injury in both models. Finally, we identified the localization of proliferating cell nuclear antigen-positive, ED-1-positive, and terminal dUTP nick-end labeled-positive cells in the hypoxic cortical area in the remnant kidney model. We propose here a possible pathological tie between chronic tubulointerstitial hypoxia and progressive glomerular diseases. (Am J

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“…A reduction in renal VEGF-A is observed in acute and chronic nondiabetic renal disease, mostly associated with a loss of glomerular and peritubular capillaries. [1][2][3][4][5] In these situations, administration of VEGF-A has been shown to improve renal histology and function. 3,4,6,7 In contrast, levels of both circulating and local VEGF-A are high in diabetes, and excessive VEGF-A has been shown to have a role in mediating glomerular hypertrophy, proteinuria, and retinopathy, 8,9 indicating that VEGF-A is deleterious in this unique situation.…”

mentioning

confidence: 99%

Selective Stimulation of VEGFR2 Accelerates Progressive Renal Disease

Sato

Tanabe

Kosugi

et al. 2011

The American Journal of Pathology

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Vascular endothelial growth factor A (VEGF-A) can play both beneficial and deleterious roles in renal diseases, where its specific function might be determined by nitric oxide bioavailability. The complexity of VEGF-A in renal disease could in part be accounted for by the distinct roles of its two receptors; VEGFR1 is involved in the inflammatory responses, whereas VEGFR2 predominantly mediates angiogenesis. Because nondiabetic chronic renal disease is associated with capillary loss, we hypothesized that selective stimulation of VEGFR2 could be beneficial in this setting. However, VEGFR2 activation may be deleterious in the presence of nitric oxide deficiency. We systematically overexpressed a mutant form of VEGF-A binding only VEGFR2 (Flk-sel) using an adeno-associated virus-1 vector in wild-type and eNOS knockout mice and then induced renal injury by uninephrectomy. Flksel treatment increased angiogenesis and lowered blood pressure in both mouse types. Flk-sel overexpression caused mesangial injury with increased proliferation associated with elevated expression of PDGF, PDGF-␤ receptor, and VEGFR2; this effect was greater in eNOS knockout than in wild-type mice. Flk-sel also induced tubulointerstitial injury, with some tubular epithelial cells expressing ␣-smooth muscle actin, indicating a phenotypic evolution toward myofibroblasts. In conclusion, prestimulation of VEGFR2 can potentiate subsequent renal injury in mice, an effect enhanced in the setting of nitric oxide deficiency.

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Impaired angiogenesis in the aging kidney: Vascular endothelial growth factor and thrombospondin-1 in renal disease

Cited by 158 publications

References 28 publications

Enhancement of in vitro human tubulogenesis by endothelial cell-derived factors: implications for in vivo tubular regeneration after injury

Enhancement of in vitro human tubulogenesis by endothelial cell-derived factors: implications for in vivo tubular regeneration after injury

Hypoxia in Renal Disease with Proteinuria and/or Glomerular Hypertension

Selective Stimulation of VEGFR2 Accelerates Progressive Renal Disease

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