PMID- 28124643
OWN - NLM
STAT- MEDLINE
DCOM- 20170421
LR  - 20211204
IS  - 1945-8932 (Electronic)
IS  - 1945-8932 (Linking)
VI  - 30
IP  - 6
DP  - 2016 Nov 1
TI  - 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.
PG  - 211-217
LID - 10.2500/ajra.2016.30.4389 [doi]
AB  - 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 ng/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.
FAU - Ko, Dong-Yn
AU  - Ko DY
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College 
      of Medicine, Seoul, South Korea This study was support.
FAU - Shin, Jae-Min
AU  - Shin JM
FAU - Um, Ji-Young
AU  - Um JY
FAU - Kang, Byungjin
AU  - Kang B
FAU - Park, Il-Ho
AU  - Park IH
FAU - Lee, Heung-Man
AU  - Lee HM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Rhinol Allergy
JT  - American journal of rhinology & allergy
JID - 101490775
RN  - 0 (ACTA2 protein, human)
RN  - 0 (Actins)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transforming Growth Factor beta)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Actins/metabolism
MH  - Cell Differentiation/drug effects/genetics
MH  - Cells, Cultured
MH  - Collagen/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Fibroblasts/*drug effects/physiology
MH  - Humans
MH  - Immunosuppressive Agents/*pharmacology
MH  - Myofibroblasts/*drug effects/physiology
MH  - Nasal Polyps/*drug therapy/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinase/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2017/01/27 06:00
MHDA- 2017/04/22 06:00
CRDT- 2017/01/27 06:00
PHST- 2017/01/27 06:00 [entrez]
PHST- 2017/01/27 06:00 [pubmed]
PHST- 2017/04/22 06:00 [medline]
AID - 10.2500/ajra.2016.30.4389 [doi]
PST - ppublish
SO  - Am J Rhinol Allergy. 2016 Nov 1;30(6):211-217. doi: 10.2500/ajra.2016.30.4389.