title: Protective effect of Ac-SDKP on alveolar epithelial cells through inhibition of EMT via TGF-β1/ROCK1 pathway in silicosis in rat.
abstract: The epithelial-mesenchymal transition (EMT) is a critical stage during the development of silicosis fibrosis. In the current study, we hypothesized that the anti-fibrotic tetrapeptide, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) may exert its anti-fibrotic effects via activation of the TGF-β1/ROCK1 pathway, leading to inhibition of EMT. To address this hypothesis, we first examined the effect of Ac-SDKP upon EMT using an in vivo rat silicosis model, as well as in an in vitro model of TGF-β1-induced EMT. Confocal laser scanning microscopy was used to examine colocalization of surfactant protein A (SP-A), fibroblast specific protein-1 (FSP-1) and α-smooth muscle actin (α-SMA) in vivo. Western blot analysis was used to examine for changes in the protein levels of E-cadherin (E-cad) and SP-A (epithelial cell markers), vimentin (mesenchymal cell marker), α-SMA (active myofibroblast marker), and collagen I and III in both in vivo and in vitro experiments. Secondly, we utilized Western blot analysis and confocal laser scanning microscopy to examine the protein expression of TGF-β1 and ROCK1 in in vivo and in vitro studies. The results revealed that Ac-SDKP treatment prevented increases in the expression of mesenchymal markers as well as TGF-β1, ROCK1, collagen I and III. Furthermore, Ac-SDKP treatment prevented decreases in the expression of epithelial cell markers in both in vivo and in vitro experiments. Based on the results, we conclude that Ac-SDKP inhibits the transition of epithelial cell-myofibroblast in silicosis via activation of the TGF-β1/ROCK1 signaling pathway, which may serve as a novel mechanism by which it exerts its anti-fibrosis properties.
authors.affiliation: School of Basic Medical Sciences, North China University of Science and Technology, Tangshan, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Deng
authors.affiliation: Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Pathology Department, Hebei Medical University, Shi Jiazhuang, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
authors.forename: Darrell
authors.initials: D
authors.lastname: Brann
authors.affiliation: Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, China. Electronic address: fangyang1978@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D006801:Humans; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012829:Silicosis / Q000473:pathology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; D009842:Oligopeptides; D020011:Protective Agents; D037662:Pulmonary Surfactant-Associated Protein A; D053773:Transforming Growth Factor beta1; D054460:rho-Associated Kinases; C579666:FSP1 protein, rat; C498862:Acta2 protein, rat; C578418:ROCK1 protein, rat; C058504:goralatide
keywords: Epithelial–mesenchymal transition; N-acetyl-seryl-aspartyl-lysyl-proline; Silicosis; TGF-β1/ROCK1 pathway; Type II alveolar epithelial cells