Calmodulin-myosin light chain kinase inhibition changes fibroblast-populated collagen lattice contraction, cell migration, focal adhesion formation, and wound contraction.

Published

Journal Article

Wound healing requires fibroblast migration, synthesis of new extracellular matrix, and organization of that matrix, all of which depend upon myosin ATPase activation and subsequent cytoplasmic actin-myosin contraction. Myosin ATPase activity is optimized by phosphorylation of myosin light chain at serine 19. Several different signaling pathways can perform that phosphorylation, the focus here is calcium saturated calmodulin dependent -myosin light chain kinase (CaM-MLCK). It is proposed that CaM-MLCK phosphorylation of myosin light chain and subsequent myosin ATPase activation affects granulation tissue fibroblast behavior and contributes to wound contraction. Myosin ATPase activity generates actin-myosin contraction within fibroblasts. Myosin ATPase activity is involved in ATP-induced cell contraction, the generation of focal adhesions, fibroblast migration, fibroblast populated collagen lattice (FPCL) contraction, and wound contraction. The MLCK inhibitors ML-9 and ML-7 inhibited ATP-induced cell contraction, fibroblast migration, FA formation, and FPCL contraction. The calmodulin inhibitors W7 and fluphenazine blocked rat open wound contraction. In addition, fluphenazine delayed re-epithelialization. These findings support the idea that fibroblast CaM-MLCK activity is essential for tissue repair. We speculate that inhibition of CaM-MLCK may reduce or prevent detrimental fibrotic contracture.

Full Text

Duke Authors

Cited Authors

  • Levinson, H; Moyer, KE; Saggers, GC; Ehrlich, HP

Published Date

  • September 2004

Published In

Volume / Issue

  • 12 / 5

Start / End Page

  • 505 - 511

PubMed ID

  • 15453832

Pubmed Central ID

  • 15453832

International Standard Serial Number (ISSN)

  • 1067-1927

Digital Object Identifier (DOI)

  • 10.1111/j.1067-1927.2004.012502.x

Language

  • eng

Conference Location

  • United States