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Toxicol Lett. 2016 Nov 16;262:161-172. doi: 10.1016/j.toxlet.2016.10.004. Epub 2016 Oct 4.

Emodin alleviates bleomycin-induced pulmonary fibrosis in rats.

Author information

1
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
2
Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
3
Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
4
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention, Fudan University, Shanghai 200032, China. Electronic address: llshen@shmu.edu.cn.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease with few treatment options and poor prognosis. Emodin, extracted from Chinese rhubarb, was found to be able to alleviate bleomycin (BLM)-induced pulmonary fibrosis, yet the underlying mechanism remains largely unknown. This study aimed to further investigate the effects of emodin on the inflammation and fibrosis of BLM-induced pulmonary fibrosis and the mechanism involved in rats. Our results showed that emodin improved pulmonary function, reduced weight loss and prevented death in BLM-treated rats. Emodin significantly relieved lung edema and fibrotic changes, decreased collagen deposition, and suppressed the infiltration of myofibroblasts [characterized by expression of α-smooth muscle actin (α-SMA)] and inflammatory cells (mainly macrophages and lymphocytes). Moreover, emodin reduced levels of TNF-α, IL-6, TGF-β1 and heat shock protein (HSP)-47 in the lungs of BLM-treated rats. In vitro, emodin profoundly inhibited TGF-β1-induced α-SMA, collagen IV and fibronectin expression in human embryo lung fibroblasts (HELFs). Emodin also inhibited TGF-β1-induced Smad2/3 and STAT3 activation, indicating that Smad2/3 and STAT3 inactivation mediates emodin-induced effects on TGF-β1-induced myofibroblast differentiation. These results suggest that emodin can exert its anti-fibrotic effect via suppression of TGF-β1 signaling and subsequently inhibition of inflammation, HSP-47 expression, myofibroblast differentiation and extracellular matrix (ECM) deposition.

KEYWORDS:

Emodin; Extracellular matrix deposition; Heat shock protein-47; Inflammation; Myofibroblast differentiation; Pulmonary fibrosis

PMID:
27717887
DOI:
10.1016/j.toxlet.2016.10.004
[Indexed for MEDLINE]

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