Baricitinib Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice by Inhibiting TGF-β1 Signaling Pathway

被引：22

作者：

Gu, Songtao ^{[1
]}

Liang, Jingjing ^{[2
,3
,4
]}

Zhang, Jianwei ^{[2
,3
,4
]}

Liu, Zhichao ^{[2
,3
]}

Miao, Yang ^{[2
,3
]}

Wei, Yuli ^{[2
,3
,4
]}

Li, Shimeng ^{[2
,3
,4
]}

Gu, Jinying ^{[5
]}

Cui, Yunyao ^{[5
]}

Xiao, Ting ^{[2
,3
,4
]}

Li, Xiaohe ^{[2
,3
,4
]}

Yang, Cheng ^{[2
,3
,4
]}

机构：

[1] Tianjin Chest Hosp, Dept Resp & Crit Care Med, 261 Taierzhuang South Rd, Tianjin 300222, Peoples R China

[2] Nankai Univ, Coll Pharm, State Key Lab Med Chem Biol, Haihe Educ Pk, 38 Tongyan Rd, Tianjin 300353, Peoples R China

[3] Nankai Univ, Tianjin Key Lab Mol Drug Res, Haihe Educ Pk, 38 Tongyan Rd, Tianjin 300353, Peoples R China

[4] Tianjin Int Joint Acad Biomed, Tianjin Key Lab Mol Drug Res, Tianjin 300457, Peoples R China

[5] Tianjin Jikun Technol Co Ltd, Tianjin 301700, Peoples R China

来源：

MOLECULES | 2023年 / 28卷 / 05期

基金：

中国国家自然科学基金;

关键词：

pulmonary fibrosis; baricitinib; TGF-beta 1 signaling pathway; JAK-STAT; GROWTH-FACTOR-BETA; TGF-BETA; PATHOGENESIS; MECHANISMS;

D O I：

10.3390/molecules28052195

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with unknown etiology, high mortality and limited treatment options. It is characterized by myofibroblast proliferation and extensive deposition of extracellular matrix (ECM), which will lead to fibrous proliferation and the destruction of lung structure. Transforming growth factor-beta 1 (TGF-beta 1) is widely recognized as a central pathway of pulmonary fibrosis, and the suppression of TGF-beta 1 or the TGF-beta 1-regulated signaling pathway may thus offer potential antifibrotic therapies. JAK-STAT is a downstream signaling pathway regulated by TGF-beta 1. JAK1/2 inhibitor baricitinib is a marketed drug for the treatment of rheumatoid arthritis, but its role in pulmonary fibrosis has not been reported. This study explored the potential effect and mechanism of baricitinib on pulmonary fibrosis in vivo and in vitro. The in vivo studies have shown that baricitinib can effectively attenuate bleomycin (BLM)-induced pulmonary fibrosis, and in vitro studies showed that baricitinib attenuates TGF-beta 1-induced fibroblast activation and epithelial cell injury by inhibiting TGF-beta 1/non-Smad and TGF-beta 1/JAK/STAT signaling pathways, respectively. In conclusion, baricitinib, a JAK1/2 inhibitor, impedes myofibroblast activation and epithelial injury via targeting the TGF-beta 1 signaling pathway and reduces BLM-induced pulmonary fibrosis in mice.

引用

页数：19

共 38 条

[1] Baricitinib: A Review in Rheumatoid Arthritis [J].

Al-Salama, Zaina T. ;

Scott, Lesley J. .

DRUGS, 2018, 78 (07) :761-772

[2] The effect of drugs used in rheumatology for treating SARS-CoV2 infection [J].

Atzeni, Fabiola ;

Gerratana, Elisabetta ;

Giallanza, Manuela ;

La Corte, Laura ;

Nucera, Valeria ;

Miceli, Gianfranco ;

Sangari, Donatella ;

Masala, Ignazio Francesco .

EXPERT OPINION ON BIOLOGICAL THERAPY, 2021, 21 (02) :219-228

[3] The potential of JAK/STAT pathway inhibition by ruxolitinib in the treatment of COVID-19 [J].

Bagca, Bakiye Goker ;

Avci, Cigir Biray .

CYTOKINE & GROWTH FACTOR REVIEWS, 2020, 54 :51-61

[4] Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis [J].

Chakraborty, Debomita ;

Sumova, Barbora ;

Mallano, Tatjana ;

Chen, Chih-Wei ;

Distler, Alfiya ;

Bergmann, Christina ;

Ludolph, Ingo ;

Horch, Raymund E. ;

Gelse, Kolja ;

Ramming, Andreas ;

Distler, Oliver ;

Schett, Georg ;

Senolt, Ladislav ;

Distler, Jorg H. W. .

NATURE COMMUNICATIONS, 2017, 8

[5] Baricitinib as rescue therapy in a patient with COVID-19 with no complete response to sarilumab [J].

Cingolani, A. ;

Tummolo, A. M. ;

Montemurro, G. ;

Gremese, E. ;

Larosa, L. ;

Cipriani, M. C. ;

Pasciuto, G. ;

Liperoti, R. ;

Murri, R. ;

Pirronti, T. ;

Cauda, R. ;

Fantoni, M. .

INFECTION, 2020, 48 (05) :767-771

[6]

Denton CP, 2007, ARTHRITIS RHEUM-US, V56, P323, DOI 10.1002/art.22289

[7] Discovery of 9O-Substituted Palmatine Derivatives as a New Class of Anti-COL1A1 Agents Via Repressing TGF-β1/Smads and JAK1/STAT3 Pathways [J].

Fan, Tianyun ;

Ge, Maoxu ;

Guo, Zhihao ;

He, Hongwei ;

Zhang, Na ;

Li, Yinghong ;

Song, Danqing .

MOLECULES, 2020, 25 (04)

[8] Non-canonical (non-SMAD2/3) TGF-β signaling in fibrosis: Mechanisms and targets [J].

Finnson, Kenneth W. ;

Almadani, Yasser ;

Philip, Anie .

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 2020, 101 :115-122

[9] Idiopathic pulmonary fibrosis: Molecular mechanisms and potential treatment approaches [J].

Glass, Daniel S. ;

Grossfeld, David ;

Renna, Heather A. ;

Agarwala, Priya ;

Spiegler, Peter ;

Kasselman, Lora J. ;

Glass, Amy D. ;

DeLeon, Joshua ;

Reiss, Allison B. .

RESPIRATORY INVESTIGATION, 2020, 58 (05) :320-335

[10] The Aging Lung and Idiopathic Pulmonary Fibrosis [J].

Gulati, Swati ;

Thannickal, Victor J. .

AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 2019, 357 (05) :384-389

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