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From the Department of Pathology,*
Centre Médical
Universitaire, University of Geneva, Geneva; and the Department
of Surgery,
Geneva University Hospital,
Geneva, Switzerland
We have examined the role of mechanical tension in myofibroblast
differentiation using two in vivo rat models. In the
first model, granulation tissue was subjected to an increase in
mechanical tension by splinting a full-thickness wound with a plastic
frame. Myofibroblast features, such as stress fiber
formation, expression of ED-A fibronectin and 
-smooth muscle
actin (-SMA) appeared earlier in splinted than in unsplinted wounds.
Myofibroblast marker expression decreased in control wounds starting at
10 days after wounding as expected, but persisted in splinted
wounds. In the second model, granuloma pouches were induced by
subcutaneous croton oil injection; pouches were either left intact or
released from tension by evacuation of the exudate at 14 days. The
expression of myofibroblast markers was reduced after tension release
in the following sequence: F-actin (2 days), -SMA (3
days), and ED-A fibronectin (5 days); cell density was not
affected. In both models, isometric contraction of tissue
strips was measured after stimulation with smooth muscle agonists.
Contractility correlated always with the level of -SMA
expression, being high when granulation tissue had been
subjected to tension and low when it had been relaxed. Our results
support the assumption that mechanical tension is crucial for
myofibroblast modulation and for the maintenance of their contractile
activity.
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