Tanshinone IIA ameliorates bleomycin-induced pulmonary fibrosis and inhibits transforming growth factor-beta-β-dependent epithelial to mesenchymal transition.
BACKGROUND
Epithelial to mesenchymal transition (EMT) of alveolar epithelial cells occurs in lung fibrotic diseases. Tanshinone IIA (Tan IIA) has been reported to exert anti-inflammatory effects in pulmonary fibrosis. Nonetheless, whether Tan IIA affects lung fibrosis-related EMT remains unknown and requires for further investigations.


METHODS
A single intratracheal instillation of saline containing bleomycin (BLM; 5 mg/kg body weight) was performed to induce pulmonary fibrosis in Sprague-Dawley rats. Rats receiving an instillation of equivoluminal normal saline served as controls. Then, these rats were given a daily intraperitoneal administration of Tan IIA (15 mg/kg body weight) for 28 d before sacrifice. In vitro, recombinant transforming growth factor-beta 1 (TGF-β1; 10 ng/mL) was used to treat human alveolar epithelial A549 cells for 48 h. Tan IIA (10 μM) or control DMSO was used to pretreat cells for 2 h before TGF-β1 stimulation. Rat lung tissue samples and A549 cells were then subjected to further assessments.


RESULTS
Tan IIA was noted to alleviate BLM-induced pulmonary collagen deposition and macrophage infiltration in rats. Epithelial-cadherin expression was decreased after BLM stimulation, whereas α-smooth muscle actin, fibronectin, and vimentin were increased. These expression alterations were partially reversed by Tan IIA. Moreover, Tan IIA suppressed BLM-induced increases in TGF-β1, phosphorylated Smad-2, and -3 in rats. Additionally, pretreatment of Tan IIA inhibited TGF-β1-triggered EMT, reduced collagen Ⅰ production, and blocked TGF-β signal transduction in A549 cells.


CONCLUSIONS
Our research suggests that Tan IIA mitigates BLM-induced pulmonary fibrosis and suppresses TGF-β-dependent EMT of lung alveolar epithelial cells.
Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Haiying
H
Tang
Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Huanyu
H
He
Department of Pediatrics, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Hong
H
Ji
Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Lili
L
Gao
Department of Gastroenterology, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Jingwei
J
Mao
Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China.
Jia
J
Liu
Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China. Electronic address: linhongli@vip.163.com.
Hongli
H
Lin
Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian, People's Republic of China. Electronic address: wutaihua@sina.com.
Taihua
T
Wu
D045784:Abietanes / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C021751:tanshinone; D001761:Bleomycin
Epithelial to mesenchymal transition; Pulmonary fibrosis; TGF-β signaling pathway; Tanshinone ⅡA