[Inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline on myofibroblast differentiation by regulating acetylated tubulin α in silicotic rat model].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
; 33(11): 816-21, 2015 Nov.
Article
em Zh
| MEDLINE
| ID: mdl-26887263
ABSTRACT
OBJECTIVE:
To explore the inhibition effect and mechanism of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP)on myofibroblast differentiation via regulating acetylated tubulin α (Ac-Tub α)in vivo and in vitro.METHODS:
Silicotic model were made by SiO2 douched and divided into 6 groups as follows control (4w, 8w)group, silicotic model (4w, 8w)group and post-or pre-treatment by Ac-SDKP group. Pulmonary fibroblasts were divided into 5 groups (1) control; (2) Ang II; (3) Ang II+Ac-SDKP; (4) Ang II+Valsartan; (5) Ang II+TCS histone deacetylase (HDAC)6 20b. The localization of Ac-Tub α and α-smooth muscle actin (SMA) were observed by immunohistochemical (IHC) and immunofluorescence staining. The protein levels of Ac-Tub α, α-SMA, collagen type I (col I) and HDAC6 were measured by western blot.RESULTS:
In silicotic nodules and interstitial fibrosis area, positive expression of α-SMA, a classical marker of myofibroblast, was ob-served by IHC, accompanied with absence expression of Ac-Tub α. Furthermore, Ac-SDKP post-treatment could attenuate the levels of col I, α-SMA and HDAC6 to 48.39%, 52.63% and 70.18% compared with the silicotic 8w group respectively. And in Ac-SDKP pre-treatment group, compared with the silicotic 8w group, these protein levels were decreased to 32.26%, 64.91% and 54.39% respectively (P<0.05). The up-regulation of Ac-Tub α was found in Ac-SDKP post-and pre-treatment and increased to 3.00 and 2.90 folds compared with the silicotic 8w group. Compared with control group, the levels of α-SMA, HDAC6 and col I in Ang II group were up-regulated to 1.66, 3.56 and 4.00 folds accompanied with down-regulation of Ac-Tub by 44.44% (P<0.05). Pre-treatment with Valsartan, TCS HDAC6 20b or Ac-SDKP could inhibited all this changes induced by Ang II in vitro.CONCLUSION:
Ac-SDKP can inhibit the myofibroblast differentiation and collagen deposition via sup-press HDAC6 and up-regulate the expression of Ac-Tub α in vivo and in vitro.
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Bases de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Silicose
/
Tubulina (Proteína)
/
Diferenciação Celular
/
Miofibroblastos
Limite:
Animals
Idioma:
Zh
Revista:
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
Assunto da revista:
MEDICINA OCUPACIONAL
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
China