Thumbnail
Access Restriction
Open

Author Deng, Haijing ♦ Xu, Hong ♦ Zhang, Xianghong ♦ Sun, Yue ♦ Wang, Ruimin ♦ Brann, Darrell ♦ Yang, Fang
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ ACTIN ♦ COLLAGEN ♦ FIBROBLASTS ♦ FIBROSIS ♦ IN VITRO ♦ IN VIVO ♦ INHIBITION ♦ LASERS ♦ MICROSCOPY ♦ MUSCLES ♦ PNEUMOCONIOSES ♦ PROLINE ♦ RATS ♦ SURFACTANTS
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. - Highlights: • EMT is a critical stage during the development of silicosis fibrosis. • Ac-SDKP inhibits the EMT process in silicosis both in vivo and in vitro. • Ac-SDKP inhibits the EMT process in silicosis via TGF-β1/ROCK1 pathway.
ISSN 0041008X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-03-01
Publisher Place United States
Journal Toxicology and Applied Pharmacology
Volume Number 294


Open content in new tab

   Open content in new tab