UVB-induced activation and internalization of keratinocyte growth factor receptor

Marchese, Cinzia; Maresca, Vittoria; Cardinali, Giorgia; Belleudi, Francesca; Ceccarelli, Simona; Bellocci, M.; Frati, Luigi; Torrisi, Maria Rosaria; Picardo, Mauro

doi:10.1038/sj.onc.1206301

Cited by 56 publications

(49 citation statements)

References 33 publications

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“…6). Reactive oxygen species (ROS) can activate growth factor receptors and stimulate subsequent internalization and degradation (22). Increased production of ROS in response to hyperoxia thus could stimulate degradation and turnover of FGFRs, thereby contributing to the effects that we observed.…”

Section: Discussionmentioning

confidence: 69%

Altered Expressions of Fibroblast Growth Factor Receptors and Alveolarization in Neonatal Mice Exposed to 85% Oxygen

Park

Rieger‐Fackeldey

Schanbacher³

et al. 2007

Pediatr Res

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ABSTRACT:In the present study, we tested the hypothesis that exposure of newborn mice to sublethal hyperoxia would alter lung development and expressions of fibroblast growth factor receptors (FGFRs)-3 and FGFR-4. Newborn FVB mice were exposed to 85% O 2 or maintained in room air for up to 14 d. No animal mortality was observed, and body weight gains were not affected by hyperoxia. At postnatal d 7 and 14 (P7, P14), lungs of mice exposed to 85% O 2 showed fewer alveolar secondary crests and larger alveoli or terminal air spaces than did mice in room air. In pups kept in room air, lung levels of FGFR-3 and FGFR-4 mRNA were greater at P3 than at P1, but similar increases were not observed in hyperoxic mice. Immunoreactivity of FGFR-3 and FGFR-4 was lower in lungs of hyperoxic mice than in controls at P14. In pups kept in room air, lung fibroblast growth factor (FGF)-7 mRNA levels were greater at P14 than at P1, but similar changes were not observed in hyperoxic mice. The temporally and spatially specific alterations in the expressions of FGFR-3, FGFR-4, and FGF-7 in the mice exposed to hyperoxia may contribute to aberrant lung development. B ronchopulmonary dysplasia (BPD) was described initially as lung injury-and repair-related effects that were associated with radiologic findings of streaky, fibrous densities, alternating with hyperlucent areas (1,2). The primary risk factors were premature birth, respiratory distress, mechanical ventilation, and administration of supplemental oxygen (FIO 2 Ͼ0.21). Inflammation, problems in nutritional support, and comorbid conditions also contribute to the development of BPD. Modifications of therapeutic strategies have decreased the incidence of BPD, as the disease was described originally, but the overall incidence of BPD has not declined. The "new BPD" of recent years shows little acute injury and repair described by Northway et al. (1,2), but is characterized by fewer and larger alveoli and less organized alveolar vascularization, suggesting arrested or disordered lung development. The events occurring during secondary septation of terminal gas exchange units and maturation of alveolar microvasculature are therefore of particular interest in research on mechanisms responsible for the new BPD (3-8).Lung development in humans normally progresses through sequential structural changes that are observed similarly in rats and mice, which, at term, exhibit lungs that structurally resemble human lungs at 26 -30 wk of gestation (9). Infants born at this age frequently encounter respiratory problems, arising from immature pulmonary surfactant metabolism, respiratory drive and coordination, or other deficiencies. Prematurely delivered nonhuman primate models of BPD may mimic human development more closely than do rodent models, but practical constraints limit the investigations that can be explored with primate models (4,5,10).The lungs of newborn rodents are sufficient for extrauterine life and are adequate for maturation into normal adult lungs. Studies in rats and mice indicate th...

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Section: Discussionmentioning

confidence: 69%

Altered Expressions of Fibroblast Growth Factor Receptors and Alveolarization in Neonatal Mice Exposed to 85% Oxygen

Park

Rieger‐Fackeldey

Schanbacher³

et al. 2007

Pediatr Res

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“…One of the initial cellular events after UV radiation is activation of cell-surface receptors such as the EGFR 27,32,43 and KGFR. 31 In the current investigation we provide evidence that implicates cell-surface receptors (eg, EGFR) as potential transmitters of the extracellular UV signal and we refer to this as a ligand-independent event. Although the binding of EGFR ligands is also a likely mechanism of enhancing MMP-1 expression in our cell culture model, we provide convincing preliminary evidence that argue against a ligand-dependent event.…”

Section: Discussionmentioning

confidence: 97%

“…One of the earliest events in response to UV radiation involves ligand-independent autophosphorylation of cell surface growth factor receptors such as the keratinocyte growth factor receptor (KGFR) 31 and the epidermal growth factor receptor (EGFR). 32 It is highly likely that stimulation of such receptors by UV contributes to the activation of MAPK pathways.…”

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confidence: 99%

Epidermal Growth Factor Receptor Signaling Is Partially Responsible for the Increased Matrix Metalloproteinase-1 Expression in Ocular Epithelial Cells after UVB Radiation

Girolamo

Coroneo

Wakefield

2005

The American Journal of Pathology

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Pterygia are inflammatory, invasive, and proliferative lesions of the human ocular surface in which the matrix metalloproteinase (MMP) collagenase-1 (MMP-1) is highly expressed. Pterygia development may involve MMP-1 activity against interstitial fibrillar collagen, an abundant extracellular matrix component of the cornea, and its induction by ultraviolet light (UVB). We examined the pathways responsible for enhanced expression of MMP-1 in pterygium epithelial cells after UVB exposure and/or treatment with chemical inhibitors of mitogen-activated protein kinases or epidermal growth factor receptor. The induction of MMP-1 by UVB was comparable to that mediated by heparin-binding epidermal growth factor-like growth factor and epidermal growth factor. The epidermal growth factor receptor inhibitor PD153035 partially blocked the UVB-mediated induction of MMP-1 and totally abrogated its production after stimulation with either heparin-binding epidermal growth factor-like growth factor or epidermal growth factor. UVB exposure enhanced the phosphorylated form of ERK1/2 in a time-dependent manner whereas the ERK1/2 inhibitor PD98059 decreased this induction by at least fivefold. Transcripts for c-jun and c-fos were detected as early as 2 hours after UVB exposure and were suppressed by PD98059. The identification of a specific intracellular signaling pathway responsible for the enhanced production of a key enzyme that denatures intact fibrillar collagen has important implications for understanding the pathophysiology and future therapy for pterygia. Pterygium is a condition of the ocular surface characterized by squamous cell metaplasia and goblet cell hyperplasia. The lesion consists of a wing-shaped mass of fibrovascular conjunctival tissue that invades the normal cornea. Other obvious pathological changes include activation of stromal fibroblasts, a persistent inflammatory component, elastotic degeneration, and destruction of collagenous barriers such as Bowman's layer. Pterygia are particularly prevalent in heavily sun-exposed individuals in whom extensive epidemiological studies link this disease to excessive ultraviolet (UV) radiation. 1-5 Despite this evidence, there is still controversy regarding the actual trigger for the development of pterygia and whether or not there is a genetic predisposition to this disease. 6 Recently, we have identified UVB as an environmental agent likely to be responsible for initiating molecular events that lead to the formation of pterygia. 7,8 From our hypothesis, 9 we postulate that UVB radiation activates cells at or near the limbus. This activation may cause 1) phenotypic alterations in a distinct population of epithelial cells, 2) production of proinflammatory and angiogenic cytokines 7 and growth factors, 8 and 3) increased invasiveness due to enhanced production of matrix metalloproteinases (MMPs) over and above their natural tissue inhibitors (TIMPs). 6,9 -12 To date, we 6,9 -12 and others [13][14][15][16][17] have accumulated data from in vitro culture and in vivo tissue-b...

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“…It remains to be determined whether electrophilic products of lipid peroxidation, such as 4-hydroxy-2-nonenal (Feng et al, 2004), which are generated in response to UV irradiation, are involved in the protective effect of KGF under these circumstances or if KGF-induced UV protection involves different mechanisms. For example, it has recently been shown that UVB irradiation induces FGFR2IIIb phosphorylation and activation via the generation of ROS, followed by receptor endocytosis (Marchese et al, 2003;Belleudi et al, 2005). This UVB-induced FGFR2IIIb activation caused apoptosis and cell-cycle arrest (Belleudi et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents

Braun

Krampert²,

Bodó

et al. 2006

Journal of Cell Science

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Owing to its potent cytoprotective properties for epithelial cells, keratinocyte growth factor (KGF) is successfully used for the treatment of chemotherapy- and radiotherapy-induced oral mucositis in cancer patients. It is therefore of major interest to determine possible clinical applications of KGF in other organs and in different stress situations and to unravel common and organ-specific mechanisms of KGF action. Here we show that KGF protects human keratinocytes from the toxicity of xenobiotics with electrophilic and oxidative properties and reduces the cell death induced by UV irradiation. In contrast to other cell types, cytoprotection of keratinocytes by KGF is not a direct anti-apoptotic effect but requires de novo protein synthesis. The in vitro findings are clinically relevant because KGF protected keratinocytes in organ-cultured human scalp hair follicles from the toxicity of the xenobiotic menadione. Moreover, injection of KGF into murine back skin markedly reduced cell death in the epidermis after UVB irradiation. This activity is dependent on FGF receptor signaling because it was abrogated in transgenic mice expressing a dominant-negative FGF receptor mutant in keratinocytes. Taken together, our results encourage the use of KGF for skin protection from chemical and physical insults.

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UVB-induced activation and internalization of keratinocyte growth factor receptor

Cited by 56 publications

References 33 publications

Altered Expressions of Fibroblast Growth Factor Receptors and Alveolarization in Neonatal Mice Exposed to 85% Oxygen

Altered Expressions of Fibroblast Growth Factor Receptors and Alveolarization in Neonatal Mice Exposed to 85% Oxygen

Epidermal Growth Factor Receptor Signaling Is Partially Responsible for the Increased Matrix Metalloproteinase-1 Expression in Ocular Epithelial Cells after UVB Radiation

Keratinocyte growth factor protects epidermis and hair follicles from cell death induced by UV irradiation, chemotherapeutic or cytotoxic agents

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