TET1 Regulates Nestin Expression and Human Airway Smooth Muscle Proliferation.
Am J Respir Cell Mol Biol
; 71(4): 420-429, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-38861343
ABSTRACT
Asthma is characterized by aberrant airway smooth muscle (ASM) proliferation, which increases the thickness of the ASM layer within the airway wall and exacerbates airway obstruction during asthma attacks. The mechanisms that drive ASM proliferation in asthma are not entirely elucidated. Ten-eleven translocation methylcytosine dioxygenase (TET) is an enzyme that participates in the regulation of DNA methylation by catalyzing the hydroxylation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC). The generation of 5-hmC disinhibits the gene silencing effect of 5-mC. In this study, TET1 activity and protein were enhanced in asthmatic human ASM cell cultures. Moreover, the concentration of 5-hmC was higher in asthmatic ASM cells than in nonasthmatic ASM cells. Knockdown (KD) of TET1, but not TET2, reduced the concentration of 5-hmC in asthmatic cells. Because the cytoskeletal protein nestin controls cell proliferation by modulating mTOR, we evaluated the effects of TET1 KD on this pathway. TET1 KD reduced nestin expression in ASM cells. In addition, TET1 inhibition alleviated the platelet-derived growth factor-induced phosphorylation of p70S6K, 4E-BP, S6, and Akt. TET1 inhibition also attenuated the proliferation of ASM cells. Taken together, these results suggest that TET1 drives ASM proliferation via the nestin-mTOR axis.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Asma
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Proteínas Proto-Oncogénicas
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Miocitos del Músculo Liso
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Proliferación Celular
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Nestina
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Oxigenasas de Función Mixta
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
/
Am. j. respir. cell mol. biol
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American journal of respiratory cell and molecular biology
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article