PMID- 18086923
OWN - NLM
STAT- MEDLINE
DCOM- 20080128
LR  - 20220310
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Print)
IS  - 0021-9525 (Linking)
VI  - 179
IP  - 6
DP  - 2007 Dec 17
TI  - Myofibroblast contraction activates latent TGF-beta1 from the extracellular 
      matrix.
PG  - 1311-23
AB  - The conjunctive presence of mechanical stress and active transforming growth 
      factor beta1 (TGF-beta1) is essential to convert fibroblasts into contractile 
      myofibroblasts, which cause tissue contractures in fibrotic diseases. Using 
      cultured myofibroblasts and conditions that permit tension modulation on the 
      extracellular matrix (ECM), we establish that myofibroblast contraction functions 
      as a mechanism to directly activate TGF-beta1 from self-generated stores in the 
      ECM. Contraction of myofibroblasts and myofibroblast cytoskeletons prepared with 
      Triton X-100 releases active TGF-beta1 from the ECM. This process is inhibited 
      either by antagonizing integrins or reducing ECM compliance and is independent 
      from protease activity. Stretching myofibroblast-derived ECM in the presence of 
      mechanically apposing stress fibers immediately activates latent TGF-beta1. In 
      myofibroblast-populated wounds, activation of the downstream targets of TGF-beta1 
      signaling Smad2/3 is higher in stressed compared to relaxed tissues despite 
      similar levels of total TGF-beta1 and its receptor. We propose activation of 
      TGF-beta1 via integrin-mediated myofibroblast contraction as a potential 
      checkpoint in the progression of fibrosis, restricting autocrine generation of 
      myofibroblasts to a stiffened ECM.
FAU - Wipff, Pierre-Jean
AU  - Wipff PJ
AD  - Laboratory of Cell Biophysics, Ecole Polytechnique Federale de Lausanne, CH-1015 
      Lausanne, Switzerland.
FAU - Rifkin, Daniel B
AU  - Rifkin DB
FAU - Meister, Jean-Jacques
AU  - Meister JJ
FAU - Hinz, Boris
AU  - Hinz B
LA  - eng
GR  - P01 AR049698/AR/NIAMS NIH HHS/United States
GR  - R01 CA034282/CA/NCI NIH HHS/United States
GR  - AR49698/AR/NIAMS NIH HHS/United States
GR  - CA34282/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Integrins)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, rat)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, rat)
RN  - 0 (Transforming Growth Factor beta1)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytoskeleton/physiology
MH  - Extracellular Matrix/*metabolism
MH  - Fibroblasts/*physiology/ultrastructure
MH  - Integrins/physiology
MH  - Muscle Contraction/*physiology
MH  - Myoblasts, Smooth Muscle/*physiology/ultrastructure
MH  - Phosphorylation
MH  - Rats
MH  - Smad2 Protein/metabolism
MH  - Smad3 Protein/metabolism
MH  - Stress, Mechanical
MH  - Transforming Growth Factor beta1/*metabolism
MH  - Wound Healing/physiology
PMC - PMC2140013
EDAT- 2007/12/19 09:00
MHDA- 2008/01/29 09:00
PMCR- 2008/06/17
CRDT- 2007/12/19 09:00
PHST- 2007/12/19 09:00 [pubmed]
PHST- 2008/01/29 09:00 [medline]
PHST- 2007/12/19 09:00 [entrez]
PHST- 2008/06/17 00:00 [pmc-release]
AID - jcb.200704042 [pii]
AID - 200704042 [pii]
AID - 10.1083/jcb.200704042 [doi]
PST - ppublish
SO  - J Cell Biol. 2007 Dec 17;179(6):1311-23. doi: 10.1083/jcb.200704042.