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 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.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, P.R. China. Electronic address: countryspring@sina.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, P.R. China. Electronic address: 413499057@qq.com.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Ji
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, P.R. China. Electronic address: davidjiangwl@163.com.
authors.forename: Zechun
authors.initials: Z
authors.lastname: Kang
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, P.R. China. Electronic address: Lucky_lcj@sina.com.
authors.forename: Changjun
authors.initials: C
authors.lastname: Lv
authors.affiliation: School of Pharmaceutical Sciences, Binzhou Medical University, Yantai, P.R. China. Electronic address: jwl518@163.com.
authors.forename: Wanglin
authors.initials: W
authors.lastname: Jiang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001547:Benzaldehydes / Q000494:pharmacology* / Q000627:therapeutic use*; D001761:Bleomycin; D002396:Catechols / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D000199:Actins; D001547:Benzaldehydes; D001761:Bleomycin; D002396:Catechols; D003094:Collagen; D016222:Fibroblast Growth Factor 2; D024243:HMGB1 Protein; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D053773:Transforming Growth Factor beta1; C585491:HMGB1 protein, human; C104200:Hbp1 protein, rat; C498862:Acta2 protein, rat; C005581:protocatechualdehyde
keywords: Epithelial–mesenchymal transition; Fibroblast growth factor 2; High mobility group box 1; Protocatechuic aldehyde; Pulmonary fibrosis; Receptor for advanced glycation end-product