Integrin-linked kinase: a possible role in scar contracture.

Abstract

Integrin-linked kinase (ILK) participates with beta1 integrin to mediate extracellular matrix interactions, such as extracellular matrix reorganization. Thus, ILK is hypothesized to influence wound contraction and scar contracture and, as such, would be a target molecule to manipulate pharmacologically in expediting wound contraction or possibly preventing scar contracture. The expression of ILK messenger ribonucleic acid, along with ILK-protein expression, was found in fibroblasts. The localization of ILK in human skin and rat granulation tissue was documented by immunohistology. ILK was present in human dermal fibroblasts, but was not found in human epidermal cells in skin. Cells were transfected with wild-type ILK or kinase-deficient ILK (E359K) and were assayed for collagen lattice contraction, migration, and myosin adenosine triphosphatase (ATPase) activity. Cells overexpressing E359K were poorer at collagen lattice contraction than control cells, whereas cells overexpressing wild-type ILK were equal to control cells at lattice contraction. ILK overexpression enhanced cell migration, but E359K overexpression did not affect cell migration. Neither ILK nor E359K overexpression altered myosin ATPase activity. Hence, ILK action within fibroblasts appears unrelated to myosin ATPase control of microfilament-generated forces. ILK appears to be a target molecule for pharmacologic manipulation to expedite wound contraction or to prevent scar contracture.