title: Emodin alleviates bleomycin-induced pulmonary fibrosis in rats.
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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Guan
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Song
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xianxia
authors.initials: X
authors.lastname: Yan
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Linlin
authors.initials: L
authors.lastname: Shen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001761:Bleomycin / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004642:Emodin / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects; D050958:HSP47 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation / Q000473:pathology / Q000517:prevention & control; D008297:Male; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012129:Respiratory Function Tests; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D016207:Cytokines; D004791:Enzyme Inhibitors; D050958:HSP47 Heat-Shock Proteins; D001761:Bleomycin; D004642:Emodin
keywords: Emodin; Extracellular matrix deposition; Heat shock protein-47; Inflammation; Myofibroblast differentiation; Pulmonary fibrosis