Doxycycline Attenuates Paraquat-induced Pulmonary Fibrosis by Downregulating the TGF-β Signaling Pathway

Overview

Journal J Thorac Dis

Publisher AME Publishing Company

Specialty Pulmonary Medicine

Date 2017 Dec 23

PMID 29268507

Citations 8

Authors

Xu-Fang Hua

Xiao-He Li

Mi-Mi Li

Cheng-yu Zhang

Hui-juan Liu

Tao Sun

Hong-gang Zhou

Cheng Yang

Affiliations

Soon will be listed here.

Abstract

Background: Paraquat (PQ) is a highly efficient herbicide that remains widely used in agriculture. However, the inappropriate application of this herbicide may cause multiple organ injuries including pulmonary injury. In this study, we report that doxycycline (Doxy) treats PQ-induced pulmonary fibrosis (PF).

Methods: Mice with PQ-induced PF were treated with different doses of Doxy by intragastric administration. Human lung cancer cell line A549 pre-treated with TGF-β1 (5 ng/mL) were treated with Doxy hydrochloride (3.4 µM).

Results: PF was observed from day 28 in PQ-treated group and Doxy treatments significantly reduced pulmonary coefficient, histopathological score and collagen content in a dose-dependent manner. Doxy can inhibit the expression levels of plasma inflammation cytokines at day 28 after modeling and reduced inflammatory response at early stage of PQ-induced lung injury. Immunohistochemical staining assay and proteomic analysis indicated that Doxy could restore ectopic epithelial-mesenchymal transition (EMT) induced by PQ-treatment by regulating numerous TGF-β signaling related proteins.

Conclusions: The findings suggest that Doxy can restore the balance of epithelial-mesenchymal cells and attenuate PQ-induced PF by downregulating the TGF-β signaling pathway.

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