title: Ac-SDKP suppresses epithelial-mesenchymal transition in A549 cells via HSP27 signaling.
abstract: The synthetic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has been shown to be a modulator of molecular aspects of the fibrosis pathway. This study reveals that Ac-SDKP exerts an anti-fibrotic effect on human type II alveolar epithelial cells (A549), which are a source of myofibroblasts once exposed to TGF-β1, by decreasing the expression of heat shock protein 27 (HSP27). We used A549 cells in vitro to detect morphological evidence of epithelial-mesenchymal transition (EMT) by phase-contrast microscopy. Immunocytochemical and western blot analysis determined the distributions of cytokeratin 8 (CK8), α-smooth muscle actin (α-SMA), and SNAI1. Confocal laser scanning microscopy revealed a colocalization of HSP27 and SNAI1 on TGF-β1-induced A549 cells. These results also demonstrated that A549 cells became spindle-like when exposed to TGF-β1. Coincident with these morphological changes, expression levels of CK8 and E-cad decreased, while those of vimentin and α-SMA increased. This process was accompanied by increases in levels of HSP27, SNAI1, and type I and type III collagen. In vitro transfection experiments demonstrated that the inhibition of HSP27 in cultured A549 cells could decrease the expression of SNAI1 and α-SMA while increasing the expression of E-cad. A noticeable reduction in collagen types I and III was also evident. Our results found that Ac-SDKP inhibited the transition of cultured A549 cells to myofibroblasts and attenuated collagen synthesis through modulating the expression of HSP27.
authors.affiliation: Pathology Department, Hebei Medical University, Shi Jiazhuang, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Deng
authors.affiliation: Pathology Department, Hebei Medical University, Shi Jiazhuang, China; Medical Research Center, Hebei United University, Tangshan, China. Electronic address: fangyang1978@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Xue
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Shipu
authors.initials: S
authors.lastname: Du
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Shifeng
authors.initials: S
authors.lastname: Li
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Medical Research Center, Hebei United University, Tangshan, China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D058628:Myofibroblasts / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D016827:CD8 Antigens; D015820:Cadherins; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009842:Oligopeptides; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D003094:Collagen; C058504:goralatide
keywords: Epithelial–mesenchymal transition; Heat shock protein 27; Myofibroblasts; N-acetyl-seryl-aspartyl-lysyl-proline; Type II alveolar epithelial cells