Klotho modulates ER-mediated signaling crosstalk between prosurvival autophagy and apoptotic cell death during LPS challenge.
Apoptosis
; 24(1-2): 95-107, 2019 02.
Article
en En
| MEDLINE
| ID: mdl-30357572
ABSTRACT
Bacterial endotoxins have been shown to induce prosurvival autophagy or apoptosis in fibroblasts and thus impair the wound healing process. Endoplasmic reticulum has been proposed as a molecular switch between these processes and klotho protein possessing pleiotropic characteristics seems to be involved in both processes, however the exact molecular mechanism is unknown. In this study, we have evaluated the effect of klotho silencing on human fibroblasts exposed to a non-toxic dose of lipopolysaccharide in terms of in vitro wound healing ability. We show for the first time, that klotho silencing in fibroblasts intensified lipopolysaccharide-induced oxidative stress and inflammatory response, what resulted in genomic instability, p-eIF2a-mediated ER stress, retardation of prosurvival autophagy, induction of apoptotic cell death and finally in impaired wound closure. Therefore, our data suggest that klotho serves as a part of cellular defense mechanism engaged in providing protection against bacterial infections during wound healing by modulating ER-signaling crosstalk between autophagy and apoptosis.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
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Lipopolisacáridos
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Apoptosis
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Retículo Endoplásmico
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Estrés del Retículo Endoplásmico
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Glucuronidasa
Límite:
Humans
Idioma:
En
Año:
2019
Tipo del documento:
Article