Effects of RNA interference-induced Smad3 gene silencing on pulmonary fibrosis caused by paraquat in mice

Experimental Biology and Medicine
Xue-Song DongZhi Liu

Abstract

Paraquat (PQ) poisoning induces many physiological and histological changes in the human body, but PQ-induced pulmonary fibrosis is most often associated with death. The signaling pathway associated with pulmonary fibrosis is reliant on transforming growth factor-beta 1 (tgf-β(1)) activation of Smad3, as evidenced by Smad3-deficient mice being resistant to tgf-β(1)-induced pulmonary fibrosis. Thus, we sought to determine whether targeted silencing of Smad3 gene expression could inhibit PQ-induced pulmonary fibrosis in mice. We developed an RNA interference (RNAi) method using short hairpin RNAs (shRNAs) targeting Smad3. The shRNA expression cassettes capable of effectively silencing Smad3 in L929 mouse fibroblasts were transferred to an adenovirus vector and intratracheally administered into mouse lung. Treated mice presented with inhibited Smad3 mRNA and protein and were resistant to PQ-induced pulmonary fibrosis, as evidenced by suppressed expressions of procollagen type I mRNA and hydroxyproline amino acid. Thus, silencing of Smad3 appears to be a promising alternative strategy for the treatment of PQ-induced pulmonary fibrosis.

References

Mar 1, 1990·The American Review of Respiratory Disease·J Kelley
Jan 1, 1987·The Journal of Experimental Medicine·A E PostlethwaiteA H Kang
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·S M WahlP E Klotman
Jul 7, 1999·The Journal of Clinical Investigation·A NakaoI Iwamoto
Dec 28, 1999·Microbes and Infection·G S Ashcroft
Feb 13, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jingsong ZhaoDavid Warburton
Apr 18, 2002·Genes & Development·Patrick J PaddisonDouglas S Conklin
Jun 8, 2002·Biochemical and Biophysical Research Communications·Yun Zhao, Dawn A Geverd
Jul 12, 2002·Nature·Gregory J Hannon
Aug 27, 2002·Archives of Environmental Health·Kyu-Yoon HwangSae-Yong Hong
Mar 26, 2003·FEBS Letters·Changxian ShenSven N Reske
May 22, 2003·American Journal of Physiology. Renal Physiology·Constance E RunyanAnne-Christine Poncelet
Feb 11, 2004·Chest·Ulrike Bartram, Christian P Speer
Jun 16, 2004·Experimental Lung Research·David A GronebergJochen Springer
Jul 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Philippe BonniaudJack Gauldie
Aug 31, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·N VenkatesanM S Ludwig
Jun 27, 2006·Proceedings of the American Thoracic Society·Dean Sheppard
Jul 21, 2006·Toxicology·Guy MainwaringJonathan G Moggs
Jan 12, 2007·Toxicology·Masafumi TomitaTakaki Ishikawa
Jan 20, 2007·Biochemical and Biophysical Research Communications·Asish K GhoshJohn Varga
Feb 17, 2007·Acta Pharmacologica Sinica·Li GuXin-Lun Tian
Jun 15, 2007·Free Radical Biology & Medicine·R J Dinis-OliveiraF Carvalho
Sep 25, 2007·Journal of Plastic, Reconstructive & Aesthetic Surgery : JPRAS·Zimin WangYouxin Jin
Dec 25, 2007·BMC Public Health·David GunnellFlemming Konradsen
Jun 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marilyn J GrosRodolphe R Guinamard
Dec 28, 2010·Cytokine·Laura ArribillagaEsperanza Feijoó

❮ Previous
Next ❯

Citations

Jan 8, 2014·Drug and Chemical Toxicology·Lingjie XuZhong Wang
Nov 26, 2015·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Linshen XieLijun Peng
Nov 7, 2016·Biochemical and Biophysical Research Communications·Fei YangLi Zhu
Sep 18, 2013·Laboratory Investigation; a Journal of Technical Methods and Pathology·Xiaodong SongChangjun Lv
Aug 12, 2016·International Journal of Molecular Medicine·Yi-Chun WangQu-Lian Guo
Feb 23, 2021·Molecular Therapy. Methods & Clinical Development·Mitchel J R RuigrokWouter L J Hinrichs
Apr 10, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Lu YangJiang Deng

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
fluorescence microscopy
flow cytometry
protein assay

Software Mentioned

SPSS

Related Concepts

Related Feeds

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.