The regulation of matrix deposition is a key event in many physiological and pathological situations. It involves the activity of mediators in autocrine and paracrine fashions and the contact of cells with the surrounding extracellular matrix as well. The tightly regulated balance of both mechanisms guarantees rapid and adaptive cellular responses to meet changes in the biological requirements of the environment. Disturbances lead to wound healing defects or the development of fibrosis. The molecular mechanisms for these regulatory events are only partially understood, but involve the activity of integrins and a structural continuum of extracellular matrix-receptor-cytoskeleton-nucleus for transfer of information and the regulation of activated genes.