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BBB Seminar: Beate Eckes

Crucial role for integrin-linked kinase in fibroblast functions

Beate Eckes, Department of Dermatology, University of Cologne, Germany.

The extracellular matrix is a key regulator of cell functions, e.g. proliferation, differentiation and migration. Binding of matrix macromolecules to integrins initiates the assembly of an intracellular multiprotein complex, the focal adhesion, of which integrin-linked kinase (ILK) is a central component. ILK binds to the intracellular tail of β1 integrins and recruits adaptor proteins, thus connecting the outside environment to the actin cytoskeleton.

Here, we report the generation of an inducible fibroblast-specific ILK-deficient mouse. ILK-deficient skin fibroblasts show impaired cell spreading, focal adhesion assembly and stress fiber formation on collagen and fibronectin substrates. Transduction of mechanical forces was reduced, as ILK-null fibroblasts show a greatly impaired capacity to contract collagen lattices. In line with altered mechanical properties and with the observation that ILK-deficient fibroblasts show reduced TGF-β secretion, the expression of α-smooth muscle actin was diminished, indicating that myofibroblast differentiation was hampered. Moreover, migration was impaired, most likely due to overactivity of RhoA and reduced Rac.

Since all of the before mentioned processes are pivotal for proper tissue repair, we wounded fibroblast-specific ILK-deficient and control animals. Fibroblast-specific ILK-deficient animals show strongly reduced wound contraction and greatly disturbed granulation tissue formation. Fewer myofibroblasts were present in the granulation tissue. In conclusion, ILK plays an important role in fibroblasts in sensing environmental cues, in regulating RhoA activity and TGF-β levels and thereby contributes to dermal homeostasis.

Host: Donald Gullberg , Department of Biomedicine