title: Low-dose paclitaxel ameliorates pulmonary fibrosis by suppressing TGF-β1/Smad3 pathway via miR-140 upregulation.
abstract: Abnormal TGF-β1/Smad3 activation plays an important role in the pathogenesis of pulmonary fibrosis, which can be prevented by paclitaxel (PTX). This study aimed to investigate an antifibrotic effect of the low-dose PTX (10 to 50 nM in vitro, and 0.6 mg/kg in vivo). PTX treatment resulted in phenotype reversion of epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AECs) with increase of miR-140. PTX resulted in an amelioration of bleomycin (BLM)-induced pulmonary fibrosis in rats with reduction of the wet lung weight to body weight ratios and the collagen deposition. Our results further demonstrated that PTX inhibited the effect of TGF-β1 on regulating the expression of Smad3 and phosphorylated Smad3 (p-Smad3), and restored the levels of E-cadherin, vimentin and α-SMA. Moreover, lower miR-140 levels were found in idiopathic pulmonary fibrosis (IPF) patients, TGF-β1-treated AECs and BLM-instilled rat lungs. Through decreasing Smad3/p-Smad3 expression and upregulating miR-140, PTX treatment could significantly reverse the EMT of AECs and prevent pulmonary fibrosis of rats. The action of PTX to ameliorate TGF-β1-induced EMT was promoted by miR-140, which increased E-cadherin levels and reduced the expression of vimentin, Smad3 and p-Smad3. Collectively, our results demonstrate that low-dose PTX prevents pulmonary fibrosis by suppressing the TGF-β1/Smad3 pathway via upregulating miR-140.
authors: Department of Clinical Medicine, Binzhou Medical University, Yantai, China.
authors: Congjie
authors: C
authors: Wang
authors: Xiaodong
authors: X
authors: Song
authors: Youjie
authors: Y
authors: Li
authors: Fang
authors: F
authors: Han
authors: Shuyan
authors: S
authors: Gao
authors: Xiaozhi
authors: X
authors: Wang
authors: Shuyang
authors: S
authors: Xie
authors: Changjun
authors: C
authors: Lv
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D017239:Paclitaxel / Q000008:administration & dosage; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D050257:Tubulin Modulators / Q000008:administration & dosage; D015854:Up-Regulation
chemical_list: C580706:MIRN140 microRNA, rat; D035683:MicroRNAs; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D050257:Tubulin Modulators; D001761:Bleomycin; D017239:Paclitaxel
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