Coordinated regulation of procollagens I and III and their post-translational enzymes by dissipation of mechanical tension in human dermal fibroblasts

Mechanical tension governs fibroblast proliferation and survival and the ho meostasis of the extracellular matrix to adapt its resistance to the mechan ical requirements of the organs. To consolidate this view, we analysed the effect of tension release on the expression of molecules involved in the ar chitecture and stabilisation of the collagen fibres, namely the procollagen s type I and III, the amino- and carboxy-procollagen peptidases (N-pCP and C-pCP) and lysyl oxidase. Cells were cultured in conditions of high mechani cal stress in monolayer on a collagen coat and under reduced tension by dis ruption of the cytoskeleton upon treatment with cytochalasin D in monolayer on a collagen coat or by integrin-mediated stress relaxation in a freely r etracting collagen gel. The mRNAs were measured by quantitative RT-PCR moni tored by simultaneous reverse-transcription and amplification of an origina l internal standard. Tension relaxation resulted in a decreased expression of the procollagens type I and III, of the two expressed forms of C-pCP, of the two forms of N-pCP and of lysyl oxidase. Type III collagen, known to c ontrol diameter of the fibres, was less down-regulated than type I collagen . Interestingly, the expression of the two alternatively spliced forms of t he N-pCP was dissimilarly regulated. These data suggest that mechanical ten sion may modulate the stiffness of the extracellular matrix by controlling not only the level of expression of its fibrillar constituents but also tha t of the enzymes participating in their extracellular processing and mechan ical stabilisation.