Tectorigenin inhibits the in vitro proliferation and enhances miR-338* expression of pulmonary fibroblasts in rats with idiopathic pulmonary fibrosis.
Tectorigenin is one of the main components in rhizomes of Iris tectorum, which is traditionally used to treat disorders such as hepatic cirrhosis caused by fibrosis. Idiopathic pulmonary fibrosis (IPF), one of the most common interstitial lung diseases, is caused by accumulation of fibroblasts in lungs.


OBJECTIVE
In this work we sought to examine the effects of tectorigenin on pulmonary fibroblasts in the IPF animal model and investigated the molecular mechanism (microRNA regulation) of tectorigenin treatment.


METHODS
A well-known animal disease model of pulmonary fibrosis in rat was established by intratracheally instilling of bleomycin. In vitro cultured pulmonary fibroblasts in bleomycin-treated rats and in controls were treated with or without tectorigenin. Comparative analyses of cell proliferation, apoptosis and cell cycle of pulmonary fibroblasts in bleomycin-treated rats and in controls were performed. Expression of miR-338* and its candidate gene LPA1 related to IPF of tectorigenin-treated pulmonary fibroblasts in bleomycin-treated rats were further investigated.


RESULTS
Tectorigenin significantly inhibited the proliferation of pulmonary fibroblasts in bleomycin-treated rats but not in controls. However, no altered cell cycle and apoptosis of pulmonary fibroblasts in bleomycin-treated rats and in controls was observed after tectorigenin treatment. Tectorigenin remarkably enhanced miR-338* expression of pulmonary fibroblasts in bleomycin-treated rats and downregulated LPA1 in the protein level.


CONCLUSIONS
Tectorigenin inhibits the proliferation of pulmonary fibroblasts in vitro and enhances miR-338* expression, which might in turn downregulate LPA1. This indicates a potential inhibitory role of tectorigenin on the pathogenesis of IPF.
Zhang
Huan
H
Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.
Liu
Xiufang
X
Chen
Shi
S
Wu
Junhua
J
Ye
Xie
X
Xu
Lizhi
L
Chen
Huimei
H
Zhang
Deping
D
Tan
Renxiang
R
Wang
Yaping
Y
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology*; D007529:Isoflavones / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D006131:Growth Inhibitors; D007529:Isoflavones; C532050:MIRN338 microRNA, human; C573089:MIRN338 microRNA, rat; D035683:MicroRNAs; C120039:tectorigenin