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. A lthough the effect of tissue expansion on in vivo skin physiology and histology has been well documented, it remains unclear whether keratin ocytes or other cell types are responsible for these changes. Therefor e, we investigated the in vitro effect of cyclic (10 cycles/min, 150 m mHg) or constant (continuous, 150 mmHg) strain on human keratinocyte p henotype and relevant mechanosignaling pathways. Our results demonstra te that keratinocytes subjected to cyclic strain exhibit a significant (P < 0.05) increase in cell proliferation (49.2 +/- 15.8%), DNA synth esis (37.7 +/- 4.5%), elongation (20.3 +/- 2.7%), and protein synthesi s (17.9 +/- 6.6% increase) as compared with stationary controls. In co ntrast, keratinocytes subjected to constant strain were unaffected asi de from a modest transitory increase in the proliferative rate. Kerati nocytes 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 adenosin e mono phosphate (cAMP), protein kinase A (PKA), and prostaglandin E-2 (PCE2) as compared with stationary controls (cAMP, 30 +/- 7.5%; PKA, 45 +/- 17%, PGE(2), 58 +/- 4.3%; percent decrease vs. that of control) , We conclude that direct application of cyclic strain on human kerati nocytes modulates cell phenotype and cAMP-mediated signaling pathways in an inverse manner. Moreover, keratinocytes may play an important ro le in previously observed alterations in skin properties associated wi th tissue expansion and other strain-induced responses. (C) 1997 Wiley -Liss, Inc.