title: Emodin ameliorates bleomycin-induced pulmonary fibrosis in rats by suppressing epithelial-mesenchymal transition and fibroblast activation.
abstract: Aberrant activation of TGF-β1 is frequently encountered and promotes epithelial-mesenchymal transition (EMT) and fibroblast activation in pulmonary fibrosis. The present study investigated whether emodin mediates its effect via suppressing TGF-β1-induced EMT and fibroblast activation in bleomycin (BLM)-induced pulmonary fibrosis in rats. Here, we found that emodin induced apoptosis and inhibited cellular proliferation, migration and differentiation in TGF-β1-stimulated human embryonic lung fibroblasts (HELFs). Emodin suppressed TGF-β1-induced EMT in a dose- and time-dependent manner in alveolar epithelial A549 cells. Emodin also inhibited TGF-β1-induced Smad2, Smad3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediated the emodin-induced effects on TGF-β1-induced EMT. Additionally, we provided in vivo evidence suggesting that emodin apparently alleviated BLM-induced pulmonary fibrosis and improved pulmonary function by inhibiting TGF-β1 signaling and subsequently repressing EMT, fibroblast activation and extracellular matrix (ECM) deposition. Taken together, our data suggest that emodin mediates its effects mainly via inhibition of EMT and fibroblast activation and thus has a potential for the treatment of pulmonary fibrosis.
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Ruijuan
authors: R
authors: Guan
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Xia
authors: X
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Xiaomei
authors: X
authors: Zhao
authors: Division of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Nana
authors: N
authors: Song
authors: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Jimin
authors: J
authors: Zhu
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Jijiang
authors: J
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Jin
authors: J
authors: Wang
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Chunmei
authors: C
authors: Xia
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Yonghua
authors: Y
authors: Chen
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
authors: Danian
authors: D
authors: Zhu
authors: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.|Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention, Fudan University, Shanghai, China.
authors: Linlin
authors: L
authors: Shen
mesh_terms: D000072283:A549 Cells; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004642:Emodin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D001761:Bleomycin; D004642:Emodin