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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2013.1
- 수록면
- 437 - 444 (8page)
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Purpose: The present study was designed to determine whether rapamycin could inhibit transforming growth factor β1 (TGF-β1)-induced fibrogenesis in primary lung fibroblasts, and whether the effect of inhibition would occur through the mammalian target of rapamycin (mTOR) and its downstream p70S6K pathway. Materials and Methods: Primary normal human lung fibroblasts were obtained from histological normal lung tissue of 3 patients with primary spontaneous pneumothorax.
Growth arrested, synchronized fibroblasts were treated with TGF-β1 (10 ng/mL) and different concentrations of rapamycin (0.01, 0.1, 1, 10 ng/mL) for 24 h. We assessed m-TOR, p-mTOR, S6K1, p-S6K1 by Western blot analysis, detected type III collagen and fibronectin secreting by ELISA assay, and determined type III collagen and fibronectin mRNA levels by real-time PCR assay. Results: Rapamycin significantly reduced TGF-β1-induced type III collagen and fibronectin levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we also found that TGF-β1-induced mTOR and p70S6K phosphorylation were significantly down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the TGF-β1-mediated fibrogenic response in primary human lung fibroblasts. Conclusion: These results indicate that rapamycin effectively suppresses TGF-β1-induced type III collagen and fibronectin levels in primary human lung fibroblasts partly through the mTOR/p70S6K pathway. Rapamycin has a potential value in the treatment of pulmonary fibrosis.
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참고문헌 (34)
참고문헌 신청
Yoshioka S / 2007 / Alpha-defensin enhances expression of HSP47 and collagen-1 in human lung fibroblasts / Life Sci 80:1839~1845
Derynck R / 2003 / Smad-dependent and Smad-independent pathways in TGF-beta family signalling / Nature 425:577~584
Moustakas A / 2005 / Non-Smad TGF-beta signals / J Cell Sci 118:3573~3584
Lamouille S / 2011 / Emergence of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin axis in transforming growth factor-β-induced epithelial-mesenchymal transition / Cells Tissues Organs 193:8~22
Hartford CM / 2007 / Rapamycin: something old, something new, sometimes borrowed and now renewed / Clin Pharmacol Ther 82:381~388
Derynck R / 2003 / Smad-dependent and Smad-independent pathways in TGF-beta family signalling / Nature 425:577~584
Moustakas A / 2005 / Non-Smad TGF-beta signals / J Cell Sci 118:3573~3584
Lamouille S / 2011 / Emergence of the phosphoinositide 3-kinase-Akt-mammalian target of rapamycin axis in transforming growth factor-β-induced epithelial-mesenchymal transition / Cells Tissues Organs 193:8~22
Hartford CM / 2007 / Rapamycin: something old, something new, sometimes borrowed and now renewed / Clin Pharmacol Ther 82:381~388
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