PMID- 23364979
OWN - NLM
STAT- MEDLINE
DCOM- 20140106
LR  - 20211203
IS  - 1976-2437 (Electronic)
IS  - 0513-5796 (Print)
IS  - 0513-5796 (Linking)
VI  - 54
IP  - 2
DP  - 2013 Mar 1
TI  - Rapamycin inhibits transforming growth factor beta1-induced fibrogenesis in primary 
      human lung fibroblasts.
PG  - 437-44
LID - 10.3349/ymj.2013.54.2.437 [doi]
AB  - PURPOSE: The present study was designed to determine whether rapamycin could 
      inhibit transforming growth factor beta1 (TGF-beta1)-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-beta1 
      (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-beta1-induced type III collagen and fibronectin 
      levels, as well as type III collagen and fibronectin mRNA levels. Furthermore, we 
      also found that TGF-beta1-induced mTOR and p70S6K phosphorylation were significantly 
      down-regulated by rapamycin. The mTOR/p70S6K pathway was activated through the 
      TGF-beta1-mediated fibrogenic response in primary human lung fibroblasts. 
      CONCLUSION: These results indicate that rapamycin effectively suppresses 
      TGF-beta1-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.
FAU - Gao, Yu
AU  - Gao Y
AD  - Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, 
      Capital Medical University, 8 Gongren Tiyuchang South Road, Beijing 100020, 
      China.
FAU - Xu, Xuefeng
AU  - Xu X
FAU - Ding, Ke
AU  - Ding K
FAU - Liang, Yan
AU  - Liang Y
FAU - Jiang, Dianhua
AU  - Jiang D
FAU - Dai, Huaping
AU  - Dai H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Korea (South)
TA  - Yonsei Med J
JT  - Yonsei medical journal
JID - 0414003
RN  - 0 (Collagen Type III)
RN  - 0 (Fibronectins)
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cells, Cultured
MH  - Collagen Type III/metabolism
MH  - Fibroblasts/*drug effects/metabolism/physiology
MH  - Fibronectins/metabolism
MH  - Humans
MH  - Lung/cytology/drug effects
MH  - Pulmonary Fibrosis/drug therapy
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism/physiology
MH  - Transforming Growth Factor beta1/*antagonists & inhibitors/physiology
PMC - PMC3576000
COIS- The authors have no financial conflicts of interest.
EDAT- 2013/02/01 06:00
MHDA- 2014/01/07 06:00
PMCR- 2013/03/01
CRDT- 2013/02/01 06:00
PHST- 2013/02/01 06:00 [entrez]
PHST- 2013/02/01 06:00 [pubmed]
PHST- 2014/01/07 06:00 [medline]
PHST- 2013/03/01 00:00 [pmc-release]
AID - 201303437 [pii]
AID - 10.3349/ymj.2013.54.2.437 [doi]
PST - ppublish
SO  - Yonsei Med J. 2013 Mar 1;54(2):437-44. doi: 10.3349/ymj.2013.54.2.437.