Rapamycin inhibits transforming growth factor beta 1 induced myofibroblast differentiation via the phosphorylated- phosphatidylinositol 3-kinase mammalian target of rapamycin signal pathways in nasal polyp-derived fibroblasts
- Authors
- Ko, Dong-Yn; Shin, Jae-Min; Um, Ji-Young; Kang, Byungjin; Park, Il-Ho; Lee, Heung-Man
- Issue Date
- Nov-2016
- Publisher
- OCEAN SIDE PUBLICATIONS INC
- Citation
- AMERICAN JOURNAL OF RHINOLOGY & ALLERGY, v.30, no.6, pp.E211 - E217
- Indexed
- SCIE
SCOPUS
- Journal Title
- AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
- Volume
- 30
- Number
- 6
- Start Page
- E211
- End Page
- E217
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/87060
- DOI
- 10.2500/ajra.2016.30.4389
- ISSN
- 1945-8924
- Abstract
- Purpose: Rapamycin has antiproliferative and antifibrogenic effects in vitro and in vivo. The purpose of this study was to evaluate the effects of rapamycin on transforming growth factor (TGF) beta 1 induced myofibroblast differentiation (alpha smooth-muscle actin [SMA]), extracellular matrix production, and collagen contraction in nasal polyp-derived fibroblasts (NPDF). The underlying molecular mechanisms of rapamycin were also determined in NPDFs. Methods: NPDFs were grown in culture and transformed into myofibroblasts by using TGF beta 1 (5 mu g/mL). For cytotoxicity evaluation, a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay was used. Expression levels of alpha SMA, phosphorylated phosphatidylinositol 3-kinase (PI3K), and phosphorylated mammalian target of rapamycin (mTOR) were determined by using Western blot, reverse transcription-polymerase chain reaction, and immunofluorescence staining. The total amount of collagen was analyzed by using the Sircol collagen assay, and contractile activity was measured with a collagen gel contraction assay. Silencing mTOR with mTOR-specific small interference RNA was determined by using reverse transcription-polymerase chain reaction. Results: Whereas rapamycin (range, 0-400 nM) had no significant cytotoxic effects on TGF beta 1 induced NPDFs, it significantly reduced the expression levels of alpha-SMA in TGF beta 1 induced NPDFs in a dose-dependent manner. TGF beta 1 induced collagen production and collagen contraction were significantly inhibited by rapamycin treatment. Rapamycin also attenuated the TGF beta 1 induced activation of PI3K and mTOR, and its inhibitory effects were similar to those of mTOR silencing and a specific PI3K inhibitor. Conclusions: Rapamycin inhibited TGF beta 1 induced myofibroblast differentiation, extracellular matrix production, and collagen contraction through the PI3K/mTOR signal pathways in NPDFs.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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