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1.
Hum Mol Genet ; 28(9): 1429-1444, 2019 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-30566624

RESUMEN

Bronchopulmonary dysplasia (BPD), characterized by alveoli simplification and dysmorphic pulmonary microvasculature, is a chronic lung disease affecting prematurely born infants. Pulmonary hypertension (PH) is an important BPD feature associated with morbidity and mortality. In human BPD, inflammation leads to decreased fibroblast growth factor 10 (FGF10) expression but the impact on the vasculature is so far unknown. We used lungs from Fgf10+/- versus Fgf10+/+ pups to investigate the effect of Fgf10 deficiency on vascular development in normoxia (NOX) and hyperoxia (HOX, BPD mouse model). To assess the role of fibroblast growth factor receptor 2b (Fgfr2b) ligands independently of early developmentaldefects, we used an inducible double transgenic system in mice allowing inhibition of Fgfr2b ligands activity. Using vascular morphometry, we quantified the pathological changes. Finally, we evaluated changes in FGF10, surfactant protein C (SFTPC), platelet endothelial cell adhesion molecule (PECAM) and alpha-smooth muscle actin 2 (α-SMA) expression in human lung samples from patients suffering from BPD. In NOX, no major difference in the lung vasculature between Fgf10+/- and control pups was detected. In HOX, a greater loss of blood vessels in Fgf10+/- lungs is associated with an increase of poorly muscularized vessels. Fgfr2b ligands inhibition postnatally in HOX is sufficient to decrease the number of blood vessels while increasing the level of muscularization, suggesting a PH phenotype. BPD lungs exhibited decreased FGF10, SFTPC and PECAM but increased α-SMA. Fgf10 deficiency-associated vascular defects are enhanced in HOX and could represent an additional cause of morbidity in human patients with BPD.


Asunto(s)
Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/patología , Susceptibilidad a Enfermedades , Factor 10 de Crecimiento de Fibroblastos/deficiencia , Pulmón/irrigación sanguínea , Pulmón/metabolismo , Animales , Biomarcadores , Displasia Broncopulmonar/metabolismo , Biología Computacional/métodos , Modelos Animales de Enfermedad , Expresión Génica , Perfilación de la Expresión Génica , Genotipo , Hipoxia , Pulmón/patología , Ratones , Mutación , Neovascularización Fisiológica/genética , Consumo de Oxígeno , Fosforilación , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal
2.
J Pathol ; 241(1): 91-103, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27770432

RESUMEN

Inflammation-induced FGF10 protein deficiency is associated with bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurely born infants characterized by arrested alveolar development. So far, experimental evidence for a direct role of FGF10 in lung disease is lacking. Using the hyperoxia-induced neonatal lung injury as a mouse model of BPD, the impact of Fgf10 deficiency in Fgf10+/- versus Fgf10+/+ pups was investigated. In normoxia, no lethality of Fgf10+/+ or Fgf10+/- pups was observed. By contrast, all Fgf10+/- pups died within 8 days of hyperoxic injury, with lethality starting at day 5, whereas Fgf10+/+ pups were all alive. Lungs of pups from the two genotypes were collected on postnatal day 3 following normoxia or hyperoxia exposure for further analysis. In hyperoxia, Fgf10+/- lungs exhibited increased hypoalveolarization. Analysis by FACS of the Fgf10+/- versus control lungs in normoxia revealed a decreased ratio of alveolar epithelial type II (AECII) cells over total Epcam-positive cells. In addition, gene array analysis indicated reduced AECII and increased AECI transcriptome signatures in isolated AECII cells from Fgf10+/- lungs. Such an imbalance in differentiation is also seen in hyperoxia and is associated with reduced mature surfactant protein B and C expression. Attenuation of the activity of Fgfr2b ligands postnatally in the context of hyperoxia also led to increased lethality with decreased surfactant expression. In summary, decreased Fgf10 mRNA levels lead to congenital lung defects, which are compatible with postnatal survival, but which compromise the ability of the lungs to cope with sub-lethal hyperoxic injury. Fgf10 deficiency affects quantitatively and qualitatively the formation of AECII cells. In addition, Fgfr2b ligands are also important for repair after hyperoxia exposure in neonates. Deficient AECII cells could be an additional complication for patients with BPD. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Asunto(s)
Displasia Broncopulmonar/metabolismo , Factor 10 de Crecimiento de Fibroblastos/deficiencia , Animales , Animales Recién Nacidos , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/genética , Displasia Broncopulmonar/patología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Factor 10 de Crecimiento de Fibroblastos/genética , Factor 10 de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica/fisiología , Hiperoxia/complicaciones , Hiperoxia/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Surfactantes Pulmonares/metabolismo , ARN Mensajero/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo
6.
Case Rep Ophthalmol ; 12(3): 940-943, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35082652

RESUMEN

We report the case of a 23-year-old male who was referred to our clinic for a routine follow-up examination. The patient was treated for keratoconus 3 years ago in Colombia, where intracorneal ring segments were implanted mechanically in both eyes to improve his visual acuity. Surprisingly, we discovered a pre-descemetic placement of intracorneal ring segments, which could lead to potential complications, under circumstances. We illustrate this impressive finding with slit-lamp photography and high-resolution anterior segment OCT and advocate for the use of femtosecond laser as the method of choice for intracorneal ring segment insertion in order to provide maximal precision and safety.

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