Figure 11.

The damage sensor hypothesis explains how injurious mechanical stress is transduced into intracellular signaling events. Flux of molecules through a PMD signal that a mechanically injurious event has occurred locally and elicit changes in gene expression in the injured cell, acting ultimately to promote tissue adaptation to the mechanical stress that caused the cell injury. One candidate signal for changes in gene expression is Ca²⁺ influx, although this remains to be demonstrated experimentally. Efflux of an unknown, cytosolic inhibitor of fos expression is also consistent with the data of this paper. Early changes in gene expression are driven by an increase in fos expression and translocation of NF-κB into the nucleus. The suggestion that bFGF expression increases as a function of PMD is based on published data (Ku and D’Amore, 1993). Release of such growth factors as bFGF through PMD may also promote local adaptive responses, in both injured and neighboring cells.