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Title: Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway

Abstract

An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1more » and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.« less

Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
22465699
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 283; Journal Issue: 1; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; ALDEHYDES; APOPTOSIS; BLEOMYCIN; COLLAGEN; FIBROBLASTS; FIBROSIS; GROWTH FACTORS; HEMATOXYLIN; HUMAN POPULATIONS; IN VITRO; IN VIVO; LUNGS; MOBILITY; MUSCLES; PATHOGENESIS; PROLIFERATION; RATS; RECEPTORS

Citation Formats

Zhang, Liang, E-mail: countryspring@sina.com, Ji, Yunxia, E-mail: 413499057@qq.com, Kang, Zechun, E-mail: davidjiangwl@163.com, Lv, Changjun, E-mail: Lucky_lcj@sina.com, and Jiang, Wanglin, E-mail: jwl518@163.com. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. United States: N. p., 2015. Web. doi:10.1016/J.TAAP.2015.01.001.
Zhang, Liang, E-mail: countryspring@sina.com, Ji, Yunxia, E-mail: 413499057@qq.com, Kang, Zechun, E-mail: davidjiangwl@163.com, Lv, Changjun, E-mail: Lucky_lcj@sina.com, & Jiang, Wanglin, E-mail: jwl518@163.com. Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. United States. doi:10.1016/J.TAAP.2015.01.001.
Zhang, Liang, E-mail: countryspring@sina.com, Ji, Yunxia, E-mail: 413499057@qq.com, Kang, Zechun, E-mail: davidjiangwl@163.com, Lv, Changjun, E-mail: Lucky_lcj@sina.com, and Jiang, Wanglin, E-mail: jwl518@163.com. Sun . "Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway". United States. doi:10.1016/J.TAAP.2015.01.001.
@article{osti_22465699,
title = {Protocatechuic aldehyde ameliorates experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway},
author = {Zhang, Liang, E-mail: countryspring@sina.com and Ji, Yunxia, E-mail: 413499057@qq.com and Kang, Zechun, E-mail: davidjiangwl@163.com and Lv, Changjun, E-mail: Lucky_lcj@sina.com and Jiang, Wanglin, E-mail: jwl518@163.com},
abstractNote = {An abnormal high mobility group box 1 (HMGB1) activation and a decrease in receptor for advanced glycation end-product (RAGE) play a key role in the pathogenesis of pulmonary fibrosis. Protocatechuic aldehyde (PA) is a naturally occurring compound, which is extracted from the degradation of phenolic acids. However, whether PA has anti-fibrotic functions is unknown. In this study, the effects of PA on the transforming growth factor-β1 (TGF-β1)-mediated epithelial–mesenchymal transition (EMT) in A549 cells, on the apoptosis of human type I alveolar epithelial cells (AT I), on the proliferation of human lung fibroblasts (HLF-1) in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis in vivo were investigated. PA treatment resulted in a reduction of EMT in A549 cells with a decrease in vimentin and HMGB, an increase of E-cadherin and RAGE, a reduction of HLF-1 proliferation with a decrease of fibroblast growth factor 2 (FGF-2) and platelet-derived growth factor (PDGF). Apoptosis of AT I was attenuated with an increase of RAGE. PA ameliorated BLM-induced pulmonary fibrosis in rats with a reduction of histopathological scores and collagen deposition, and a lower FGF-2, PDGF, α-smooth muscle actin (α-SMA) and HMGB1 expression, whereas higher RAGE was found in BLM-instilled lungs. Through the decrease of HGMB1 and the regulation of RAGE, PA reversed the EMT, inhibited HLF-1 proliferation as well as reduced apoptosis in AT I, and prevented pulmonary fibrosis in vivo. Collectively, our results demonstrate that PA prevents experimental pulmonary fibrosis by modulating HMGB1/RAGE pathway. - Highlights: • PA prevents EMT, reduces the apoptosis of AT1 in vitro. • PA decreases proliferation of HLF-1, reduces PDGF and FGF expression in vitro. • PA prevents experimental pulmonary fibrosis by modulating the HMGB1/RAGE pathway.},
doi = {10.1016/J.TAAP.2015.01.001},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 283,
place = {United States},
year = {Sun Feb 15 00:00:00 EST 2015},
month = {Sun Feb 15 00:00:00 EST 2015}
}