Epidermal growth factor potentiates renal cell death in hydronephrotic neonatal mice, but cell survival in rats

Kiley, Susan C.; Thornhill, Barbara A.; Belyea, Brian; Neale, Karen; Forbes, Michael S.; Luetteke, Noreen; Lee, Dong Hoon; Chevalier, Robert L.

doi:10.1111/j.1523-1755.2005.00428.x

Cited by 26 publications

(22 citation statements)

References 50 publications

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“…[51][52][53] In conclusion, our work indicates that iNOS-derived NO is an important mediator of macrophage-induced tubular epithelial cell apoptosis in vitro and plays an important role in tubular epithelial cell apoptosis and tubulointerstitial fibrosis in vivo.…”

Section: -13mentioning

confidence: 94%

Nitric Oxide Is an Important Mediator of Renal Tubular Epithelial Cell Death in Vitro and in Murine Experimental Hydronephrosis

Kipari

Cailhier

Ferenbach

et al. 2006

The American Journal of Pathology

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Macrophages play a pivotal role in tissue injury and fibrosis during renal inflammation. Although macrophages may induce apoptosis of renal tubular epithelial cells, the mechanisms involved are unclear. We used a microscopically quantifiable co-culture assay to dissect the cytotoxic interaction between murine bone marrow-derived macrophages and Madin-Darby canine kidney cells and primary murine renal tubular epithelial cells. The induction of tubular cell apoptosis by cytokine-activated macrophages was reduced by inhibitors of nitric oxide synthase whereas tubular cell proliferation was unaffected. Furthermore, cytokine-activated macrophages derived from mice targeted for the deletion of inducible nitric oxide synthase were noncytotoxic. We then examined the role of nitric oxide in vivo by inhibiting inducible nitric oxide synthase in the model of murine experimental hydronephrosis. L-N 6 -(1-iminoethyl)-lysine was administered in the drinking water between days 5 and 7 after ureteric obstruction. Macrophage infiltration was comparable between groups, but treatment significantly inhibited tubular cell apoptosis at day 7. Tubular cell proliferation was unaffected. Inducible nitric oxide synthase blockade also reduced interstitial cell apoptosis and increased collagen III deposition. These data indicate that nitric oxide is a key mediator of macrophage-directed tubular cell apoptosis in vitro and in vivo and also modulates tubulointerstitial fibrosis.

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Section: -13mentioning

confidence: 94%

Nitric Oxide Is an Important Mediator of Renal Tubular Epithelial Cell Death in Vitro and in Murine Experimental Hydronephrosis

Kipari

Cailhier

Ferenbach

et al. 2006

The American Journal of Pathology

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“…There is evidence of an opposing effect of EGF action depending on species and the dose provided. For example, EGF acts as a survival factor in the neonatal kidney cells of the rat, but potentiates apoptosis under the same conditions in the neonatal mice (Kiley et al, 2005). Moreover, in a transfected hamster cell line expressing EGFR, a low EGF concentration promotes proliferation, whereas a high dose induces cell-cycle arrest and apoptosis (Zhao et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Santos¹,

Santos²,

Menezes³

et al. 2017

Anim Reprod

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The aims of this study were to verify the effects of Epidermal Growth Factor (EGF) on the morphology, primordial follicle activation, growth and proliferation of granulosa cells of ovine follicles cultured in situ, as well as the effect of a PI3K inhibitor on the follicular activation. Ten ovine ovaries were divided into fragments, being one fixed for histological analysis (fresh control). The remaining fragments were cultured for 7 days in control medium (α-MEM + ) alone or supplemented with EGF (1, 10, 50, 100 or 200 ng/mL). Follicles were classified as normal or atretic, as primordial or growing, and the oocyte and follicle diameters were measured. PCNA immunohistochemistry was performed in the fresh control and in treatment that showed the best results for follicular activation. Pharmacologic inhibition of PI3K activity was performed through pretreatment in media added with 50 µM LY294002 for 1 h. The percentage of normal follicles decreased (P < 0.05) after 7 days of culture in all treatments compared to the fresh control. A significant reduction in the percentage of primordial follicles and an increase (P < 0.05) in the growing ones were observed in all treatments compared to fresh control. Furthermore, both the control medium and 1 ng/mL EGF promoted an increase (P < 0.05) in follicular activation compared to other EGF treatments. The PCNA-positive cells in the EGF treatment were higher (P < 0.05) than in fresh control and α-MEM + . Pretreatment of ovarian tissue with PI3K inhibitor significantly inhibited (P < 0.05) α-MEM + -stimulated primordial follicle activation, but had no effect on EGF-stimulated activation (P > 0.05). In conclusion, PI3K pathway mediates the in vitro spontaneous activation of sheep primordial follicles. Moreover, EGF may act indirectly on follicular activation by promoting granulosa cell proliferation at 1 ng/mL, and EGF inhibited follicle activation in concentrations similar or higher than 10 ng/mL.

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“…68 The consequences of EGF signaling could be species dependent, because EGF administration during hydronephrosis potentiated renal cell death in mice but cell survival in rats. 69 ErbB Signaling: Beneficial or Detrimental to the Kidney?…”

Section: Erbb Signaling In Mechanisms Of Renal Repairmentioning

confidence: 99%

Epidermal Growth Factor Receptor Signaling in the Kidney

et al. 2008

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Signaling through epidermal growth factor (EGF) receptors (ErbB receptors; EGFRs) is important for fundamental cellular functions, such as proliferation, migration, growth, and differentiation. 1 In human biology, ErbB signaling is involved in normal growth and development, as well as in the initiation and progression of disease. Based on the aberrant expression in a variety of malignant tumors, ErbB family members have been recognized as targets in anticancer therapy and are now used in the treatment of breast and colon malignancies.Other than tumor biology, ErbB signaling is critically involved in renal electrolyte homeostasis. Moreover, ErbB family members are implicated in the development of end organ damage, as occurs in hypertension 2 and atherosclerosis. 3 Therefore, the therapeutic potential of targeting ErbB receptors and ErbB signaling pathways may go beyond the field of oncology. In this review, we report on the physiological and disease-related aspects of renal ErbB signaling, with attention to potential benefits and downsides of systemic ErbB inhibition in the healthy and diseased kidney.

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Epidermal growth factor potentiates renal cell death in hydronephrotic neonatal mice, but cell survival in rats

Abstract: EGF acts as a survival factor in the neonatal rat, but potentiates tubular cell death in the neonatal mouse. Species differences are maintained in cultured cells, suggesting that differences in EGF receptor signaling underlie these opposing effects.

Cited by 26 publications

References 50 publications

Nitric Oxide Is an Important Mediator of Renal Tubular Epithelial Cell Death in Vitro and in Murine Experimental Hydronephrosis

Nitric Oxide Is an Important Mediator of Renal Tubular Epithelial Cell Death in Vitro and in Murine Experimental Hydronephrosis

Blocking the PI3K pathway or the presence of high concentrations of EGF inhibits the spontaneous activation of ovine primordial follicles in vitro

Epidermal Growth Factor Receptor Signaling in the Kidney

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