Neohesperidin inhibits TGF-β1/Smad3 signaling and alleviates bleomycin-induced pulmonary fibrosis in mice

被引：61

作者：

Guo, Jiasen ^{[1
]}

Fang, Yinshan ^{[1
]}

Jiang, Fangxin ^{[1
]}

Li, Lian ^{[1
,2
]}

Zhou, Honggang ^{[3
]}

Xu, Xiaojun ^{[4
]}

Ning, Wen ^{[1
]}

机构：

[1] Nankai Univ, Coll Life Sci, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China

[2] Tianjin Med Univ, Resp Dept, Gen Hosp, Tianjin 300071, Peoples R China

[3] Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China

[4] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing 211198, Jiangsu, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACOLOGY | 2019年 / 864卷

基金：

中国国家自然科学基金;

关键词：

Neohesperidin; Pulmonary fibrosis; TGF-beta; 1; Fibroblast; GROWTH-FACTOR-BETA; PROTECTS; PATHOGENESIS; FIBROBLASTS; DELETION; SMAD2;

D O I：

10.1016/j.ejphar.2019.172712

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Idiopathic pulmonary fibrosis (IPF) is a fatal growing problem, with limited therapeutic options. Transforming growth factor beta 1 (TGF-beta 1) plays a critical role in many pathological processes that characterize pulmonary fibrosis. Effective and well-tolerated antifibrotic agents that interfere with TGF-beta 1 signaling would be an ideal treatment but no such treatments are available. In this study, we identified that the natural compound, neohesperidin, antagonizes TGF-beta 1/Smad3 signaling. We found that neohesperidin not only inhibited the TGF-beta 1-induced injury to alveolar epithelial cells but also decreased the TGF-beta 1-induced myofibroblast differentiation, extracellular matrix production, and fibroblast migration. Furthermore, we obtained in vivo evidence that neohesperidin treatment inhibited bleomycin-induced lung injuries and even attenuated established pulmonary fibrosis in mice. Our data suggest that neohesperidin can target the critical signaling pathway and profibrogenic responses in progressive pulmonary fibrosis and may have a potential use in treatment.

引用

页数：10

共 36 条

[1]

Agostini Carlo, 2006, Proc Am Thorac Soc, V3, P357, DOI 10.1513/pats.200601-010TK

[2]

[Anonymous], 2018, EVID BASED COMPLEMEN, DOI DOI 10.1155/2018/5962153

[3] Influence of l-rhamnosyl-d-glucosyl derivatives on properties and biological interaction of flavonoids [J].

Bellocco, Ersilia ;

Barreca, Davide ;

Lagana, Giuseppina ;

Leuzzi, Ugo ;

Tellone, Ester ;

Ficarra, Silvana ;

Kotyk, Arnost ;

Galtieri, Antonio .

MOLECULAR AND CELLULAR BIOCHEMISTRY, 2009, 321 (1-2) :165-171

[4] Pulmonary Macrophages: A New Therapeutic Pathway in Fibrosing Lung Disease? [J].

Byrne, Adam J. ;

Maher, Toby M. ;

Lloyd, Clare M. .

TRENDS IN MOLECULAR MEDICINE, 2016, 22 (04) :303-316

[5] Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice [J].

Dong, Yingying ;

Geng, Yan ;

Li, Lian ;

Li, Xiaohe ;

Yan, Xiaohua ;

Fang, Yinshan ;

Li, Xinxin ;

Dong, Siyuan ;

Liu, Xue ;

Li, Xue ;

Yang, Xiuhong ;

Zheng, Xiaohong ;

Xie, Ting ;

Liang, Jiurong ;

Dai, Huaping ;

Liu, Xinqi ;

Yin, Zhinan ;

Noble, Paul W. ;

Jiang, Dianhua ;

Ning, Wen .

JOURNAL OF EXPERIMENTAL MEDICINE, 2015, 212 (02) :235-252

[6] Connective tissue growth factor mediates transforming growth factor β-induced collagen synthesis:: downregulation by cAMP [J].

Duncan, MR ;

Frazier, KS ;

Abramson, S ;

Williams, S ;

Klapper, H ;

Huang, XF ;

Grotendorst, GR .

FASEB JOURNAL, 1999, 13 (13) :1774-1786

[7] Follistatin like-1 aggravates silicainduced mouse lung injury [J].

Fang, Yinshan ;

Zhang, Si ;

Li, Xiaohe ;

Jiang, Fangxin ;

Ye, Qiao ;

Ning, Wen .

SCIENTIFIC REPORTS, 2017, 7

[8] Emodin ameliorates bleomycin-induced pulmonary fibrosis in rats by suppressing epithelial-mesenchymal transition and fibroblast activation [J].

Guan, Ruijuan ;

Wang, Xia ;

Zhao, Xiaomei ;

Song, Nana ;

Zhu, Jimin ;

Wang, Jijiang ;

Wang, Jin ;

Xia, Chunmei ;

Chen, Yonghua ;

Zhu, Danian ;

Shen, Linlin .

SCIENTIFIC REPORTS, 2016, 6

[9] Recent Developments in Myofibroblast Biology Paradigms for Connective Tissue Remodeling [J].

Hinz, Boris ;

Phan, Sem H. ;

Thannickal, Victor J. ;

Prunotto, Marco ;

Desmouliere, Alexis ;

Varga, John ;

De Wever, Olivier ;

Mareel, Marc ;

Gabbian, Giulio .

AMERICAN JOURNAL OF PATHOLOGY, 2012, 180 (04) :1340-1355

[10] An Essential Role for Resident Fibroblasts in Experimental Lung Fibrosis Is Defined by Lineage-Specific Deletion of High-Affinity Type II Transforming Growth Factor β Receptor [J].

Hoyles, Rachel K. ;

Derrett-Smith, Emma C. ;

Khan, Korsa ;

Xu Shiwen ;

Howat, Sarah L. ;

Wells, Athol U. ;

Abraham, David J. ;

Denton, Christopher P. .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2011, 183 (02) :249-261

← 1 2 3 4 →