Acetylated α-Tubulin Regulated by N-Acetyl-Seryl-Aspartyl-Lysyl-Proline(Ac-SDKP) Exerts the Anti-fibrotic Effect in Rat Lung Fibrosis Induced by Silica

Wang Xiaojun, Liu Yan, Xu Hong, Zhang Xianghong, Li Shifeng, Xu Dingjie, Gao Xuemin, Zhang Lijuan, Zhang Bonan, Wei Zhongqiu, Wang Ruimin, Darrell Brann, Yang Fang

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Abstract

Silicosis is the most serious occupational disease in China. The objective of this study was to screen various proteins related to mechanisms of the pathogenesis of silicosis underlying the anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) using proteomic profile analysis. We also aimed to explore a potential mechanism of acetylated α-tubulin (α-Ac-Tub) regulation by Ac-SDKP. Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) were used to assess the different protein expression profiles between control and silicosis rats treated with or without Ac-SDKP. Twenty-nine proteins were identified to be potentially involved in the progression of silicosis and the anti-fibrotic effect of Ac-SDKP. Our current study finds that 1) the lost expression of Ac-Tub-α may be a new mechanism in rat silicosis; 2) treatment of silicotic rats with N-acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits myofibroblast differentiation and collagen deposition accompanied by stabilizing the expression of α-Ac-Tub in vivo and in vitro, which is related with deacetylase family member 6 (HDAC6) and α-tubulin acetyl transferase (α-TAT1). Our data suggest that α-Ac-Tub regulation by Ac-SDKP may potentially be a new anti-fibrosis mechanism.

Original languageEnglish (US)
Article number32257
JournalScientific reports
Volume6
DOIs
StatePublished - Aug 31 2016

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Xiaojun, W., Yan, L., Hong, X., Xianghong, Z., Shifeng, L., Dingjie, X., Xuemin, G., Lijuan, Z., Bonan, Z., Zhongqiu, W., Ruimin, W., Brann, D., & Fang, Y. (2016). Acetylated α-Tubulin Regulated by N-Acetyl-Seryl-Aspartyl-Lysyl-Proline(Ac-SDKP) Exerts the Anti-fibrotic Effect in Rat Lung Fibrosis Induced by Silica. Scientific reports, 6, [32257]. https://doi.org/10.1038/srep32257