alexa shRNA for Thymic Stromal Lymphopoietin: A Novel Therapeutic Approach for Pulmonary Fibrosis
ISSN: 2157-7013

Journal of Cell Science & Therapy
Open Access

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Research Article

shRNA for Thymic Stromal Lymphopoietin: A Novel Therapeutic Approach for Pulmonary Fibrosis

Tsung-Jen Hung1, Shu-Fen Liu1,2, Guo-Zheng Liu1, Pei-fang Hsieh3, Lea-Yea Chuang4, Jinn-Yuh Guh2, Chang-Chi Hsieh5, Yu-Ju Hung1,6, Yow-Ling Shiue3 and Yu-Lin Yang1,7*
1Graduate Institute of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan
2Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
3Graduate Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, Taiwan
4Department of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan
5Department of Animal Science and Biotechnology, Tunghai University
6Department of Public Health, National Taiwan University, Taipei, Taiwan
7Department of Medical Laboratory Science and Biotechnology, Chung Hwa University of Medical Technology, Tainan, Taiwan
Corresponding Author : Yang Yu-Lin
Department of Medical Laboratory Science and Biotechnology
Chung Hwa University of Medical Technology
Wen-Hwa 1st St. 89, Rende, Tainan, Taiwan
Fax: +886-6-2677250
Tel: +886-6-2677250
E-mail: [email protected]
Received August 20, 2013; Accepted September 16, 2013; Published September 18, 2013
Citation: Hung TJ, Liu SF, Liu GZ, Hsieh Pf, Chuang LY, et al. (2013) shRNA for Thymic Stromal Lymphopoietin: A Novel Therapeutic Approach for Pulmonary Fibrosis. J Cell Sci Ther 4:144. doi: 10.4172/2157-7013.1000144
Copyright: © 2013 Hung TJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
 

Abstract

Thymic stromal lymphopoietin (TSLP) was recently identified as a master switch for Th2 responses. This study discusses the role of TSLP in pulmonary fibrosis. We show that TGF-β1 (a Fibrogenic Growth Factor) up regulates TSLP proteins in human lung fibroblasts (HFL-1) on a dose- and time-course-dependent basis. Additionally, TSLP increases fibronectin expression on a dose- (1 ng/ml to 100 ng/ml) and time-course-dependent basis concomitantly with the upregulation of pSmad2/3 and Smad4, which is the essential downstream signal regulator for TGF-β. Silencing TSLP by TSLP shRNA dramatically reverses TGF-β1-induced cellular fibrosis concomitantly with the suppression of type I TGF-β receptors and pSmad2/3. Parallel results are observed in vivo. Bleomycin-treated C57BL/6 mice show intense staining for TSLP in fibrotic lung tissue by immunohistochemistry. More importantly, Sirius red and H&E staining from bleomycin-treated mice demonstrate that transfection with TSLP shRNA (by intranasal instillation) dramatically decreases both infiltration of inflammatory cells and deposition of collagen compared to the control. Moreover, a whole-body plethysmography test showed that TSLP shRNA transgenic mice significantly attenuate the increase in airway respiratory resistance induced by bleomycin. Thus, it may be possible to use TSLP shRNA as a novel therapeutic approach for treating pulmonary fibrosis by down-regulating TGF-β signal proteins.

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