Biology Reference
In-Depth Information
3.4.4 Regulation of Collagenase Expression by Collagen
Endocytic Receptors
Finally, in addition to redundant functions and integrated reaction sequences, regu-
latory events may lead to mutual dependence between different mechanisms in
collagen turnover. For example, the signaling activity of collagen-binding integrins
and the collagen-binding receptor tyrosine kinases, DDR-1 and -2, can lead to the
altered expression of MMPs [reviewed in Leitinger and Hohenester (
2007
)]. Fur-
thermore, regulation may occur at the protein localization and enzyme activity level.
Although this is still a quite open area, a recent study examined the effect of siRNA-
mediated downregulation of uPARAP/Endo180 in cultured fibrosarcoma cells. Not
surprisingly, this led to a reduced clearance of collagen in the cell culture and to the
accumulation of collagen material in the culture medium. This, however, in turn led
to an increased cell surface expression of MMP-14, an increasedMMP-14 activity and
increased activation of pro-MMP-2 (Messaritou et al.
2009
).
Acknowledgments We thank Drs. J. Silvio Gutkind and Mary Jo Danton for critically reviewing
this manuscript. This work was supported by the NIDCR Intramural Research Program, the
European Union Framework Programme 7 (project HEALTH-2007-201279) and by grants from
the Danish Cancer Society, the Danish Cancer Research Foundation, the Danish Rigshospitalet's
Research Council, and the Danish Medical Research Council.
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