title: [Inhibition effect of N-acetyl-seryl-aspartyl-lysyl-proline on myofibroblast differentiation by regulating acetylated tubulin α in silicotic rat model].
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Li
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Gao
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Dingjie
authors.initials: D
authors.lastname: Xu
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Deng
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Wei
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Jingrui
authors.initials: J
authors.lastname: Tian
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: North China University of Science and Technology, Tangshan 063000, China; E-mail: fangyang1955@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology; D008168:Lung / Q000473:pathology; D058628:Myofibroblasts / Q000166:cytology* / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D051381:Rats; D012822:Silicon Dioxide / Q000633:toxicity; D012829:Silicosis / Q000188:drug therapy*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000199:Actins; D024042:Collagen Type I; D009842:Oligopeptides; D012822:Silicon Dioxide; D014404:Tubulin; C498862:Acta2 protein, rat; C058504:goralatide