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Updated: May 14, 2026
Mechanistic Insight into the Development of TNBS-Mediated Intestinal Fibrosis and Evaluating the Inhibitory Effects of Rapamycin
Published on: September 12, 2019
Rapamycin inhibits transforming growth factor β1-induced fibrogenesis in primary human lung fibroblasts
1Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang South Road, Beijing 100020, China.
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.
Insights
Rapamycin inhibits transforming growth factor β1 (TGF-β1)-induced fibrogenesis in lung fibroblasts by targeting the mammalian target of rapamycin (mTOR)/p70S6K pathway. This suggests rapamycin
Area of Science:
- Pulmonary Medicine
- Cell Biology
- Pharmacology
Background:
- Transforming growth factor β1 (TGF-β1) is a key mediator of fibrogenesis.
- Pulmonary fibrosis is a progressive lung disease characterized by excessive extracellular matrix deposition.
- The mammalian target of rapamycin (mTOR) pathway plays a role in cellular growth and proliferation.
Purpose of the Study:
- To investigate if rapamycin inhibits TGF-β1-induced fibrogenesis in primary lung fibroblasts.
- To determine if this inhibition occurs via the mTOR/p70S6K pathway.
Main Methods:
- Primary human lung fibroblasts were treated with TGF-β1 and varying concentrations of rapamycin.
- Western blot analysis was used to assess mTOR and p70S6K phosphorylation.
- ELISA and real-time PCR were employed to quantify type III collagen and fibronectin levels and mRNA.
Main Results:
- Rapamycin significantly reduced TGF-β1-induced type III collagen and fibronectin levels and mRNA.
- Rapamycin down-regulated TGF-β1-induced phosphorylation of mTOR and p70S6K.
- The mTOR/p70S6K pathway is activated in TGF-β1-mediated fibrogenic responses.
Conclusions:
- Rapamycin effectively suppresses TGF-β1-induced fibrotic markers in lung fibroblasts.
- The mTOR/p70S6K pathway is implicated in rapamycin's inhibitory effect.
- Rapamycin shows potential therapeutic value for treating pulmonary fibrosis.
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