Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition

被引：45

作者：

Chen, Hong ^{[1
,2
,3
,4
]}

Chen, Qun ^{[6
]}

Jiang, Chun-ming ^{[7
]}

Shi, Guang-Yue ^{[8
]}

Sui, Bo-wen ^{[5
]}

Zhang, Wei ^{[5
]}

Yang, Li-zhen ^{[5
]}

Li, Zhu-ying ^{[5
]}

Liu, Li ^{[5
]}

Su, Yu-ming ^{[5
]}

Zhao, Wen-cheng ^{[7
]}

Sun, Hong-qiang ^{[7
]}

Li, Zhen-zi ^{[9
]}

Fu, Zhou ^{[1
,2
,3
]}

机构：

[1] Chongqing Med Univ, Childrens Hosp, Dept Resp Med, Minist Educ,Key Lab Child Dev & Disorders, Chongqing, Peoples R China

[2] China Int Sci & Technol Cooperat Base Child Dev, Chongqing, Peoples R China

[3] Chongqing Engn Res Ctr Stem Cell Therapy, Chongqing, Peoples R China

[4] Heilongjiang Univ Chinese Med, Affiliated Hosp 1, Dept Pediat, Harbin, Heilongjiang, Peoples R China

[5] Heilongjiang Univ Chinese Med, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China

[6] Peoples Hosp Acheng Dist, Dept Lab, Harbin, Heilongjiang, Peoples R China

[7] Harbin Med Univ, Affiliated Hosp 1, Harbin, Heilongjiang, Peoples R China

[8] Harbin Med Univ, Canc Hosp, Harbin, Heilongjiang, Peoples R China

[9] Harbin Med Univ, Harbin, Heilongjiang, Peoples R China

来源：

TOXICOLOGY LETTERS | 2018年 / 284卷

关键词：

Idiopathic pulmonary fibrosis; EMT; TGFB1; Triptolide; Paraquat; PANCREATIC-CANCER; TGF-BETA; COLON-CANCER; EMT; METASTASIS; GROWTH; TRANSFORMATION; ACTIVATION; APOPTOSIS; PATHWAY;

D O I：

10.1016/j.toxlet.2017.11.030

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Idiopathic pulmonary fibrosis (IPF) and tumor are highly similar to abnormal cell proliferation that damages the body. This malignant cell evolution in a stressful environment closely resembles that of epithelial-mesenchymal transition (EMT). As a popular EMT-inducing factor, TGE beta plays an important role in the progression of multiple diseases. However, the drugs that target TGFB1 are limited. In this study, we found that triptolide (TPL), a Chinese medicine extract, exerts an anti-lung fibrosis effect by inhibiting the EMT of lung epithelial cells. In addition, triptolide directly binds to TGE beta and subsequently increase E-cadherin expression and decrease vimentin expression. In in vivo studies, TPL improves the survival state and inhibits lung fibrosis in mice. In summary, this study revealed the potential therapeutic effect of paraquat induced TPL in lung fibrosis by regulating TGFO-dependent EMT progression.

引用

页码：1 / 9

页数：9

共 39 条

[1] Transforming Growth Factor-β in the Gastrointestinal and Hepatic Tumor Microenvironment [J].

Achyut, Bhagelu Ram ;

Yang, Li .

GASTROENTEROLOGY, 2011, 141 (04) :1167-1178

[2] Upholding a role for EMT in pancreatic cancer metastasis [J].

Aiello, Nicole M. ;

Brabletz, Thomas ;

Kang, Yibin ;

Angela Nieto, M. ;

Weinberg, Robert A. ;

Stanger, Ben Z. .

NATURE, 2017, 547 (7661) :E7-E8

[3] Targeting EMT to reverse renal fibrosis [J].

Susan J. Allison .

Nature Reviews Nephrology, 2015, 11 (10) :565-565

[4]

[Anonymous], LANCET, V386, P312

[5]

[Anonymous], CANC DISCOV, V5, pOF23

[6] EMT, cell plasticity and metastasis [J].

Chaffer, Christine L. ;

San Juan, Beatriz P. ;

Lim, Elgene ;

Weinberg, Robert A. .

CANCER AND METASTASIS REVIEWS, 2016, 35 (04) :645-654

[7] TGF-β Tumor Suppression through a Lethal EMT [J].

David, Charles J. ;

Huang, Yun-Han ;

Chen, Mo ;

Su, Jie ;

Zou, Yilong ;

Bardeesy, Nabeel ;

Iacobuzio-Donahue, Christine A. ;

Massague, Joan .

CELL, 2016, 164 (05) :1015-1030

[8] Sustained TGFβ exposure suppresses Smad and non-Smad signalling in mammary epithelial cells, leading to EMT and inhibition of growth arrest and apoptosis [J].

Gal, A. ;

Sjoeblom, T. ;

Fedorova, L. ;

Imreh, S. ;

Beug, H. ;

Moustakas, A. .

ONCOGENE, 2008, 27 (09) :1218-1230

[9] Inflammatory mechanisms are a minor component of the pathogenesis of idiopathic pulmonary fibrosis [J].

Gauldie, J .

AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2002, 165 (09) :1205-1206

[10]

George J.T., 2017, CANC RES

← 1 2 3 4 →