Effect of strain on human keratinocytes in vitro.

Tissue expansion, a technique to enlarge the skin surface area with an expandable balloon, has been widely used in reconstructive surgery. Although the effect of tissue expansion on in vivo skin physiology and histology has been well documented, it remains unclear whether keratinocytes or other cell types are responsible for these changes. Therefore, we investigated the in vitro effect of cyclic (10 cycles/min, 150 mmHg) or constant (continuous, 150 mmHg) strain on human keratinocyte phenotype and relevant mechanosignaling pathways. Our results demonstrate that keratinocytes subjected to cyclic strain exhibit a significant (P < 0.05) increase in cell proliferation (49.2+/-15.8%), DNA synthesis (37.7+/-4.5%), elongation (20.3+/-2.7%), and protein synthesis (17.9+/-6.6% increase) as compared with stationary controls. In contrast, keratinocytes subjected to constant strain were unaffected aside from a modest transitory increase in the proliferative rate. Keratinocytes subjected to cyclic strain aligned perpendicular to the force vector (24.2+/-1.6 degrees) as compared with stationary controls (40.4+/-2.2 degrees; the smaller degree indicates better alignment). We also report strain-induced reduction in the levels of cyclic adenosine mono phosphate (cAMP), protein kinase A (PKA), and prostaglandin E2 (PGE2) as compared with stationary controls (cAMP, 30+/-7.5%; PKA, 45+/-17%; PGE2, 58+/-4.3%; percent decrease vs. that of control). We conclude that direct application of cyclic strain on human keratinocytes modulates cell phenotype and cAMP-mediated signaling pathways in an inverse manner. Moreover, keratinocytes may play an important role in previously observed alterations in skin properties associated with tissue expansion and other strain-induced responses.