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 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.

• Authors: Liang Zhang, Yunxia Ji, Zechun Kang, Changjun Lv, Wanglin Jiang
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 283 Issue 1 Pg. 50-6 (Feb 15 2015) ISSN: 1096-0333 [Electronic] United States
• PMID: 25582705 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Actins
• Benzaldehydes
• Catechols
• HMGB1 Protein
• HMGB1 protein, human
• Hbp1 protein, rat
• Platelet-Derived Growth Factor
• RNA, Small Interfering
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Transforming Growth Factor beta1
• smooth muscle actin, rat
• Fibroblast Growth Factor 2
• Bleomycin
• protocatechualdehyde
• Collagen

Topics

• Actins (metabolism)
• Animals
• Apoptosis (drug effects)
• Benzaldehydes (pharmacology, therapeutic use)
• Bleomycin
• Catechols (pharmacology, therapeutic use)
• Cell Line
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Collagen (metabolism)
• Epithelial-Mesenchymal Transition (drug effects)
• Fibroblast Growth Factor 2 (metabolism)
• HMGB1 Protein (genetics, metabolism)
• Humans
• Lung (drug effects, metabolism, pathology)
• Male
• Platelet-Derived Growth Factor (metabolism)
• Pulmonary Fibrosis (chemically induced, drug therapy, metabolism, pathology)
• RNA, Small Interfering (genetics)
• Rats, Sprague-Dawley
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (metabolism)
• Signal Transduction
• Transforming Growth Factor beta1 (pharmacology)