Madsen, Daniel H6; Leonard, Daniel4; Masedunskas, Andrius4; Moyer, Amanda4; Jürgensen, Henrik Jessen7; Peters, Diane E4; Amornphimoltham, Panomwat4; Selvaraj, Arul4; Yamada, Susan S4; Brenner, David A4; Burgdorf, Sven4; Engelholm, Lars H8; Behrendt, Niels6; Holmbeck, Kenn4; Weigert, Roberto4; Bugge, Thomas H4
1 Behrendt Group, BRIC Research Groups, BRIC, Københavns Universitet2 Engelholm Group, BRIC Research Groups, BRIC, Københavns Universitet3 Behrendt Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet4 unknown5 Department of Biology, Faculty of Science, Københavns Universitet6 Behrendt Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet7 Behrendt Group, BRIC Research Groups, BRIC, Københavns Universitet8 Department of Biology, Faculty of Science, Københavns Universitet
Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase-dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process.
Journal of Cell Biology, 2013, Vol 202, Issue 6, p. 951-66