The roles of autophagy and hypoxia in human inflammatory periapical lesions.
Int Endod J
; 51 Suppl 2: e125-e145, 2018 Feb.
Article
em En
| MEDLINE
| ID: mdl-28439929
AIM: To determine the expressions of hypoxia-related [hypoxia-inducible transcription factors (HIF)-1α, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3) and phospho-adenosine monophosphate activated protein kinase (pAMPK)] and autophagy-related [microtubule-associated protein 1 light chain 3 (LC3), beclin-1 (BECN-1), autophagy-related gene (Atg)5-12, and p62] proteins in human inflammatory periapical lesions. METHODOLOGY: Fifteen samples of radicular cysts (RCs) and 21 periapical granulomas (PGs), combined with 17 healthy dental pulp tissues, were examined. Enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin (IL)-1ß cytokine; immunohistochemical (IHC) and Western blot (WB) analyses were employed to examine autophagy-related and hypoxia-related proteins. Transmission electron microscopy (TEM) was used to explore the ultrastructural morphology of autophagy in periapical lesions. Nonparametric Kruskal-Wallis tests and Mann-Whitney U-tests were used for statistical analyses. RESULTS: ELISA revealed a significantly higher (P < 0.001) IL-1ß expression in periapical lesions than in normal pulp tissue. Immunoscores of IHC expressions of pAMPK, HIF-1α, BNIP3, BECN-1 and Atg5-12 proteins in periapical lesions were significantly higher (P < 0.001) (except BECN-1) than those in normal pulp tissue. The results of IHC studies were largely compatible with those of WB analyses, where significantly higher (P < 0.05) expressions of hypoxia-related and autophagy-related proteins (except BECN-1, p62 and LC3II in WB analyses) in periapical lesions were noted as compared to normal pulp tissue. Upon TEM, ultrastructural double-membrane autophagosomes and autolysosomes were observed in PGs and RCs. CONCLUSIONS: Autophagy associated with hypoxia may play a potential causative role in the development and maintenance of inflamed periapical lesions.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Periapicais
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Autofagia
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article