CFTR modulates RPS27 gene expression using chloride anion as signaling effector
Abstract: In Cystic Fibrosis (CF), the impairment of the CFTR channel activity leads to a variety of alterations, including differential gene expression. However, the CFTR signaling mechanisms remain unclear. Recently, culturing IB3-1 CF cells under different intracellular Clconcentrations ([Cl-...
Guardado en:
| Autores principales: | , , , , |
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| Formato: | Artículo |
| Lenguaje: | Inglés |
| Publicado: |
Elsevier
2022
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| Materias: | |
| Acceso en línea: | https://repositorio.uca.edu.ar/handle/123456789/14560 |
| Aporte de: |
| Sumario: | Abstract:
In Cystic Fibrosis (CF), the impairment of the CFTR channel activity leads to a variety of
alterations, including differential gene expression. However, the CFTR signaling mechanisms
remain unclear. Recently, culturing IB3-1 CF cells under different intracellular Clconcentrations ([Cl-
]i), we observed several Cl-
-dependent genes and further characterized one
of them as RPS27. Thus, we hypothesized that Cl-
might act as a signaling effector for CFTR
signaling. Here, to test this idea, we study RPS27 expression in T84 cells modulating the
CFTR activity by using CFTR inhibitors. First, we observed that incubation of T84 cells with
increasing concentrations of the CFTR inhibitors CFTR(inh)-172 or GlyH-101 determined a
progressive increase in the relative [Cl-
]i
(using the Cl-
fluorescent probe SPQ). The [Cl-
]i
rise
was concomitant with a dose-dependent down-regulation of RPS27. These results imply that
CFTR inhibition produce Cl-
accumulation and that RPS27 expression can be modulated by
CFTR inhibition. Therefore, Cl-
behaves as a signaling effector for CFTR in the modulation
of RPS27 expression. In addition, the IL-1β receptor antagonist IL1RN or the JNK inhibitor
SP600125, both restored the down-regulation of RPS27 induced by CFTRinh-172, implying a
role of autocrine IL-1β and JNK signaling downstream of Cl-
in RPS27 modulation. |
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