title: [Anti-fibrotic role of AcSDKP through inhibition of P38MAPK pathway activity mediated transforming growth beta receptors in rat with silicosis].
abstract: OBJECTIVE
  To investigate the distribution and expression of transforming growth factor beta (TGF-β) receptors I and II, p38 mitogen-activated protein kinase (p38 MAPK), and type I and type III collagen in the lungs of rats with silicosis and cultured pulmonary fibroblasts, and to investigate the relationship of the anti-fibrosis effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) with its inhibition of TGF-β receptor-mediated p38 MAPK pathway activity.
  
  
  METHODS
  Rats were randomly divided into control group, silicosis model group, and AcSDKP treatment group (n = 10 for each group). For the model group and AcSDKP treatment group, rats were intratracheally instilled with silica to establish a silicosis model. Cultured pulmonary fibroblasts from neonatal rats were divided into control group, TGF-β1 stimulation group, TGF-β receptor inhibition group, p38 MAPK pathway inhibition group, and AcSDKP treatment group. The protein expression of TGF-β receptors I and II, p38 MAPK, and type I and type III collagen were determined by immunohistochemistry and Western blot. The mRNA expression of TGF-β receptors I and II were determined by real-time PCR. The distribution and nuclear translocation of phospho-p38 MAPK in cultured fibroblasts were determined by laser scanner confocal microscopy.
  
  
  RESULTS
  In the AcSDKP treatment group, AcSDKP reduced the expression of TGF-β receptors I and II, phospho-p38 MAPK, and type I and type III collagen to 86.12%, 41.01%, 42.63%, 89.05%, and 52.71%, respectively, of those of the silicosis model group (P < 0.05). In cultured fibroblasts, AcSDKP reduced the mRNA expression of TGF-β receptors I and II to 42.26% and 54.33%, respectively, of those of the TGF-β1 stimulation group; the protein expression of TGF-β receptors I and II, phospho-p38 MAPK, and type 1 and type III collagen was reduced to 58.14%, 51.40%, 45.6%, 58.04%, and 44.74%, respectively, of those of the TGF-β1 stimulation group. The phospho-p38 MAPK translocation from plasma to the nucleus was also inhibited; the nucleus/plasma ratio of p38 MAPK and the protein expression of type I and type III collagen were reduced to 68.60%, 58.04%, and 44.74%, respectively, of those of the TGF-β stimulation group (P < 0.05).
  
  
  CONCLUSIONS
  AcSDKP can inhibit the expression of collagen through inhibition of TGF-β receptor-mediated p38 MAPK pathway activity, and is thus able to exert anti-fibrosis effect in rats with silicosis.
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Zhongqiu
authors.initials: Z
authors.lastname: Wei
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Ma
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Wang
authors.affiliation: The Medical Research Center; Hebei United University, Tangshan 063000, China. E-mail: fangyang02@sohu.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012829:Silicosis / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D009842:Oligopeptides; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; C000625843:Tgfbr1 protein, rat; C058504:goralatide