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1.
Redox Biol ; 28: 101364, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731101

RESUMO

Inflammation is a self-defense response to protect individuals from infection and tissue damage, but excessive or persistent inflammation can have adverse effects on cell survival. Many individuals become especially susceptible to chronic-inflammation-induced sensorineural hearing loss as they age, but the intrinsic molecular mechanism behind aging individuals' increased risk of hearing loss remains unclear. FoxG1 (forkhead box transcription factor G1) is a key transcription factor that plays important roles in hair cell survival through the regulation of mitochondrial function, but how the function of FoxG1 changes during aging and under inflammatory conditions is unknown. In this study, we first found that FoxG1 expression and autophagy both increased gradually in the low concentration lipopolysaccharide (LPS)-induced inflammation model, while after high concentration of LPS treatment both FoxG1 expression and autophagy levels decreased as the concentration of LPS increased. We then used siRNA to downregulate Foxg1 expression in hair cell-like OC-1 cells and found that cell death and apoptosis were significantly increased after LPS injury. Furthermore, we used d-galactose (D-gal) to create an aging model with hair cell-like OC-1 cells and cochlear explant cultures in vitro and found that the expression of Foxg1 and the level of autophagy were both decreased after D-gal and LPS co-treatment. Lastly, we knocked down the expression of Foxg1 under aged inflammation conditions and found increased numbers of dead and apoptotic cells. Together these results suggest that FoxG1 affects the sensitivity of mimetic aging hair cells to inflammation by regulating autophagy pathways.

2.
Dis Model Mech ; 11(2)2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29361521

RESUMO

Mutations in the GJB2 gene [which encodes connexin 26 (Cx26)] are the most common causes of hereditary hearing loss in humans, and previous studies showed postnatal development arrest of the organ of Corti in different Cx26-null mouse models. To explore the pathological changes and the mechanism behind the cochlear abnormalities in these mice further, we established transgenic mouse models by conditional knockdown of cochlear Cx26 at postnatal day (P) 0 and P8. Auditory brainstem responses were recorded and the morphological features in the organ of Corti were analyzed 18 days after Cx26 knockdown. Mice in the P0 knockdown group displayed severe hearing loss at all frequencies, whereas mice in the P8 knockdown group showed nearly normal hearing. In the P8 knockdown group, the organ of Corti displayed normal architecture, and no ultrastructural changes were observed. In the P0 knockdown group, the phalangeal processes of Deiter's cells did not develop into finger-like structures, and the formation of microtubules in the pillar cells was significantly reduced; moreover, the amount of acetylated α-tubulin was reduced in pillar cells. Our results indicate that Gjb2 participates in postnatal development of the cytoskeleton in pillar cells during structural maturation of the organ of Corti. In P0 knockdown mice, the reduction in microtubules in pillar cells might be responsible for the failure of the tunnel of Corti to open, and the malformed phalangeal processes might negatively affect the supporting framework of the organ of Corti, which would be a new mechanism of Gjb2-related hearing loss.


Assuntos
Cóclea/anormalidades , Cóclea/crescimento & desenvolvimento , Conexinas/deficiência , Citoesqueleto/metabolismo , Técnicas de Silenciamento de Genes , Animais , Animais Recém-Nascidos , Contagem de Células , Cóclea/patologia , Conexinas/metabolismo , Citoesqueleto/ultraestrutura , Modelos Animais de Doenças , Perda Auditiva/patologia , Integrases/metabolismo , Camundongos Knockout , Órgão Espiral/patologia , Órgão Espiral/ultraestrutura
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 48(1): 51-6, 2016 Feb 18.
Artigo em Chinês | MEDLINE | ID: mdl-26885908

RESUMO

OBJECTIVE: To investigate the relationship between the removal time of 0.2 mm occlusal interference and the recovery of masticatory muscle mechanical hyperalgesia in rats. METHODS: Forty male Sprague-Dawley rats (200-220 g) were randomly assigned to eight groups, with five rats in each group: (1) naive group: these rats were anesthetized and their mouths were forced open for about 5 min (the same duration as the other groups), but restorations were not applied; (2) sham-occlusal interference control group: bands were bonded to the right maxillary first molars which did not interfere with occlusion; (3)occlusal interference group: 0.2 mm thick crowns were bonded to the right maxillary first molars; (4) 2, 3, 4, 5, and 6 d removal of occlusal interference groups: 0.2 mm thick crowns were bonded to the right maxillary first molars and removed on days 2, 3, 4, 5, and 6. The naive group and sham-occlusal interference control group were control groups. The other groups were experimental groups. Bilateral masticatory muscle mechanical withdrawal thresholds were tested on pre-application days 1, 2, and 3, and on post-application days 1, 3, 5, 7, 10, 14, 21 and 28. The rats were weighed on pre-application day 1 and on post-application days 1, 2, 3, 4, 5, 6, and 7. RESULTS: Between the naive group and the sham-occlusal interference control group, there was no significant difference in the masticatory muscle mechanical withdrawal threshold of bilateral temporalis and masseters at each time point. No significant difference was detected between the contralateral side and ipsilateral side in experimental groups (P>0.05). In the 2, 3, 4, and 5 d removal of occlusal interference groups, the masticatory muscle mechanical withdrawal thresholds decreased after occlusal interference and increased after removal of the crowns and recovered to the baseline on days 7, 10, 14, and 14, respectively [the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (137.46 ± 2.08) g, (139.02 ± 2.11) g, (140.40 ± 0.98) g, (138.95 ± 0.98) g, respectively]. In the 6 d removal of occlusal interference group, the masticatory muscle mechanical withdrawal threshold increased after removal of the crowns and became stable since day 14. There was a significant difference between the 6 d removal of occlusal interference group and the sham-occlusal interference group on day 28 (P<0.05), the masticatory muscle mechanical withdrawal thresholds of right masseter muscle were (131.24 ± 0.76) g and (141.34 ± 1.43) g, respectively. CONCLUSION: After removal of the 0.2 mm thick crown within 5 days, the mechanical hyperalgesia of the rats could reverse completely. The mechanical hyperalgesia of the rats could only be relieved, but not reverse completely after removal of the 0.2 mm thick crown on day 6. As the time went on, even minor occlusal interference could cause irreversible mechanical hyperalgesia of masticatory muscles. This study suggested that occlusal interference caused by dental treatment should be eliminated as soon as possible, to avoid irreversible orofacial pain.


Assuntos
Oclusão Dentária , Hiperalgesia/fisiopatologia , Músculos da Mastigação/fisiopatologia , Animais , Coroas , Masculino , Músculo Masseter , Dente Molar , Dor/prevenção & controle , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
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